SDHB (P21912) variants and mutations
SDHB (also known as P21912) is a human protein-coding gene encoding a succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial protein. It transfers electrons from succinate oxidation through iron-sulfur centers toward ubiquinone in mitochondrial complex II. Heterozygous loss-of-function variants strongly predispose to paraganglioma and pheochromocytoma and can also increase renal-tumor and gastrointestinal-stromal-tumor risk. This analysis covers 925 SDHB variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes pheochromocytoma/paraganglioma syndrome 4, hereditary pheochromocytoma-paraganglioma, and Carney-Stratakis syndrome. Example SDHB variants include M1I, M1L, and M1V.
Variant analysis overview
- Gene: SDHB
- Protein: P21912
- UniProt accession: P21912
- Organism: Homo sapiens
- Variants analyzed: 925
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 791 unspecified-consequence records; 7 frameshift variants; 1 stop retained variant; 69 synonymous variants; 3 in-frame deletions; 42 missense variants; 6 splice-region variants; 1 stop-gained variants; 5 substitution
- Prediction scores: 725 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: pheochromocytoma/paraganglioma syndrome 4, hereditary pheochromocytoma-paraganglioma, Carney-Stratakis syndrome, mitochondrial complex 2 deficiency, nuclear type 4, pheochromocytoma, gastrointestinal stromal tumor, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, paraganglioma, Cowden disease, mitochondrial complex II deficiency, nuclear type 1, hemangioblastoma.
Protein structure and variant hotspots
- Protein features: 2 domains; 12 binding sites; 2 post-translational modification sites.
- Structural context: 394 variants have structural context.
- PTM context: 4 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable SDHB variants
Examples include M1I, M1L, M1V, A2P, A2V, A3E, A3G, A3T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1131691061, ClinGen CA338230889, ClinVar RCV000492186, ClinVar RCV000550393, MetaLR 0.93, MetaSVM 1.03, Pathogenic, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- M1L (p.Met1Leu), rs1131691049, ClinGen CA338230894, ClinVar RCV000492218, ClinVar RCV000505307, MetaLR 0.91, MetaSVM 0.91, Pathogenic, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- M1V (p.Met1Val), rs1131691049, ClinGen CA338230895, ClinVar RCV003334506, ClinVar RCV006561447, MetaLR 0.91, MetaSVM 0.91, Pathogenic, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A2P (p.Ala2Pro), NCI-TCGA Cosmic COSV6496, Uncertain significance, Hereditary cancer-predisposing syndrome
- A2V (p.Ala2Val), rs199948437, ClinGen CA089676, NCI-TCGA Cosmic COSV6496, ClinVar RCV000633973, REVEL 0.62, CADD 26.50, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 4; Pheochromocytoma; Gastrointestinal st
- A3E (p.Ala3Glu), rs11203289, ClinGen CA338230876, ClinVar RCV001349303, 1000Genomes rs11203289, REVEL 0.59, CADD 24.40, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- A3G (p.Ala3Gly), rs11203289, ClinGen CA016202, ClinVar RCV000013632, ClinVar RCV000034690, REVEL 0.56, CADD 25.10, Benign/Likely benign, Gastrointestinal stromal tumor; Pheochromocytoma; Carney-Stratakis syndrome
- A3T (p.Ala3Thr), rs765429934, ClinGen CA089768, ClinVar RCV001359774, ClinVar RCV003169783, REVEL 0.58, CADD 23.00, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- A3V (p.Ala3Val), rs11203289, ClinGen CA338230874, ClinVar RCV000557203, ClinVar RCV003302799, REVEL 0.58, CADD 25.20, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- V4A (p.Val4Ala), rs776656866, ClinGen CA338230868, ClinVar RCV004508357, ClinVar RCV005216220, AlphaMissense 0.07, MetaLR 0.82, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- V4G (p.Val4Gly), ExAC rs776656866, REVEL 0.44, AlphaMissense 0.07
- V4M (p.Val4Met), rs2101551949, ClinGen CA338230872, ClinVar RCV001363027, Ensembl rs2101551949, REVEL 0.31, CADD 22.70, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- V5A (p.Val5Ala), rs760565241, ClinGen CA338230856, ClinVar RCV000804910, ClinVar RCV003472381, AlphaMissense 0.07, MetaLR 0.83, Uncertain significance, not provided; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syn
- V5F (p.Val5Phe), rs962717797, ClinGen CA338230858, ClinVar RCV000696453, gnomAD rs962717797, AlphaMissense 0.15, MetaLR 0.82, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- V5G (p.Val5Gly), rs760565241, ClinGen CA089519, ClinVar RCV000547089, ClinVar RCV001011890, REVEL 0.51, AlphaMissense 0.07, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- V5I (p.Val5Ile), gnomAD rs962717797, REVEL 0.30, AlphaMissense 0.15, Uncertain significance
- V5L (p.Val5Leu), rs962717797, ClinGen CA16609945, ClinVar RCV000473243, gnomAD rs962717797, REVEL 0.33, AlphaMissense 0.15, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- A6P (p.Ala6Pro), rs1472284221, ClinGen CA338230854, ClinVar RCV003041696, gnomAD rs1472284221, AlphaMissense 0.10, MetaLR 0.79, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A6S (p.Ala6Ser), rs1472284221, ClinGen CA338230853, ClinVar RCV001364779, ClinVar RCV002413867, REVEL 0.32, AlphaMissense 0.10, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- A6T (p.Ala6Thr), rs1570963601, ClinGen CA2582341895, ClinVar RCV003377775, REVEL 0.31, AlphaMissense 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- A6V (p.Ala6Val), gnomAD rs1249560928, REVEL 0.36, CADD 7.09, Uncertain significance, Hereditary cancer-predisposing syndrome
- L7F (p.Leu7Phe), rs2078164049, ClinGen CA1156102218, ClinVar RCV001324318, ClinVar RCV005271166, REVEL 0.36, CADD 11.60, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- L7H (p.Leu7His), rs778776844, ClinGen CA338230847, ClinVar RCV002012700, ClinVar RCV002423212, AlphaMissense 0.20, MetaLR 0.85, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- L7P (p.Leu7Pro), rs778776844, ClinGen CA089543, ClinVar RCV002424202, ClinVar RCV003234201, REVEL 0.49, AlphaMissense 0.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- L7V (p.Leu7Val), rs2078164049, ClinGen CA2573130772, ClinVar RCV001911604, ClinVar RCV004041770, REVEL 0.30, CADD 8.46, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Gastrointestinal stro
- S8C (p.Ser8Cys), ExAC rs199848267, TOPMed rs199848267, gnomAD rs199848267, REVEL 0.69, CADD 23.70, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- S8F (p.Ser8Phe), rs199848267, ClinGen CA089553, ClinVar RCV000687472, ClinVar RCV001015412, REVEL 0.68, CADD 23.90, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- S8P (p.Ser8Pro), rs777447369, ClinGen CA089549, ClinVar RCV001204755, ClinVar RCV002447060, REVEL 0.63, CADD 24.10, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- S8T (p.Ser8Thr), ExAC rs777447369, gnomAD rs777447369, REVEL 0.49, CADD 21.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- S8Y (p.Ser8Tyr), rs199848267, ClinGen CA338230843, ClinVar RCV001037637, ExAC rs199848267, REVEL 0.69, CADD 23.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- L9* (p.Leu9Ter), rs786203800, ClinGen CA015664, ClinVar RCV000167262, ClinVar RCV000505382, Pathogenic
- L9F (p.Leu9Phe), rs2101551820, ClinGen CA338230839, ClinVar RCV002009689, ClinVar RCV004947035, AlphaMissense 0.07, MetaLR 0.86, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- L9M (p.Leu9Met), rs1060503768, ClinGen CA338230842, ClinVar RCV003048571, REVEL 0.55, AlphaMissense 0.07, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- L9V (p.Leu9Val), rs1060503768, ClinGen CA16609943, ClinVar RCV000463673, ClinVar RCV003298511, AlphaMissense 0.07, MetaLR 0.85, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- R10G (p.Arg10Gly), rs2101551815, ClinGen CA338230837, ClinVar RCV003066681, ClinVar RCV005724917, REVEL 0.48, CADD 22.60, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- R10K (p.Arg10Lys), rs1570963545, ClinGen CA338230835, ClinVar RCV001017896, ClinVar RCV001873304, AlphaMissense 0.14, MetaLR 0.79, Conflicting interpretations, Gastrointestinal stromal tumor; Hereditary pheochromocytoma and paraganglioma; H
- R10S (p.Arg10Ser), rs1024111417, ClinGen CA18612443, ClinVar RCV001890192, ClinVar RCV003355603, REVEL 0.44, CADD 12.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Gastrointestinal stro
- R10W (p.Arg10Trp), Ensembl rs2101551815, Uncertain significance, Hereditary cancer-predisposing syndrome
- R11C (p.Arg11Cys), rs200868378, ClinGen CA089587, ClinVar RCV000229964, ClinVar RCV000564712, REVEL 0.53, CADD 21.80, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- R11H (p.Arg11His), rs111430410, ClinGen CA015753, ClinVar RCV000148868, ClinVar RCV000232749, REVEL 0.63, CADD 14.60, Benign/Likely benign, Carney-Stratakis syndrome; Pheochromocytoma/paraganglioma syndrome 4; Mitochondr
- R11P (p.Arg11Pro), rs111430410, ClinGen CA338230829, ClinVar RCV002695368, REVEL 0.60, CADD 17.70, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- R12L (p.Arg12Leu), rs1293365726, ClinGen CA338230816, ClinVar RCV001218884, ClinVar RCV001751416, REVEL 0.39, CADD 14.90, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- R12P (p.Arg12Pro), rs1293365726, ClinGen CA338230818, ClinVar RCV000705407, ClinVar RCV002458311, REVEL 0.49, CADD 16.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- R12Q (p.Arg12Gln), rs1293365726, ClinGen CA338230821, ClinVar RCV001050705, ClinVar RCV002451208, REVEL 0.36, CADD 14.20, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Pheochromocytoma/paragang
- R12W (p.Arg12Trp), rs761996626, ClinGen CA338230823, ClinVar RCV000566006, ClinVar RCV000822512, REVEL 0.36, CADD 13.80, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 4; Pheochromocytoma; Gastrointestinal st
- L13F (p.Leu13Phe), rs201745731, ClinGen CA10581755, ClinVar RCV000227644, TOPMed rs201745731, AlphaMissense 0.06, MetaLR 0.79, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- L13V (p.Leu13Val), Ensembl rs1570963512
- L13W (p.Leu13Trp), TOPMed rs1052232356
- P14L (p.Pro14Leu), rs764089231, ClinGen CA089608, ClinVar RCV000633975, ClinVar RCV002331129, REVEL 0.32, CADD 19.30, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 4; Pheochromocytoma; Gastrointestinal st
- P14Q (p.Pro14Gln), rs764089231, ClinGen CA338230756, ClinVar RCV002046965, ExAC rs764089231, REVEL 0.33, CADD 19.10, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- P14S (p.Pro14Ser), rs2101551766, ClinGen CA338230760, ClinVar RCV002756411, Ensembl rs2101551766, REVEL 0.29, CADD 13.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- A15H (p.Ala15His), rs2101551748, ClinGen CA2573130767, ClinVar RCV001975219, ClinVar RCV005421070, Pathogenic
- A15P (p.Ala15Pro), rs1553179337, ClinGen CA645369146, ClinVar RCV000492594, Ensembl rs1553179337, Pathogenic
- A15S (p.Ala15Ser), rs1553179340, ClinGen CA308156, ClinVar RCV001921860, ClinVar RCV004041214, REVEL 0.33, CADD 8.74, Pathogenic
- A15T (p.Ala15Thr), gnomAD rs1409902974, REVEL 0.35, CADD 12.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- A15V (p.Ala15Val), TOPMed rs796475064, REVEL 0.27, CADD 13.70, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- T16A (p.Thr16Ala), rs1433760506, ClinGen CA338230706, ClinVar RCV000814800, ClinVar RCV002336686, REVEL 0.35, AlphaMissense 0.08, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Carney
- T16I (p.Thr16Ile), rs775350144, ClinGen CA338230700, ClinVar RCV000821339, ExAC rs775350144, AlphaMissense 0.15, MetaLR 0.83, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- T16P (p.Thr16Pro), rs1433760506, ClinGen CA338230711, ClinVar RCV000544948, ClinVar RCV006287201, AlphaMissense 0.08, MetaLR 0.84, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- T16R (p.Thr16Arg), rs775350144, ClinGen CA089631, ClinVar RCV000456714, ClinVar RCV000574048, REVEL 0.40, AlphaMissense 0.15, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; not specified
- T17A (p.Thr17Ala), rs1060503756, ClinGen CA16609953, NCI-TCGA Cosmic COSV6496, ClinVar RCV000468636, REVEL 0.60, CADD 0.15, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- T17I (p.Thr17Ile), rs138979875, ClinGen CA089635, ClinVar RCV000532549, ClinVar RCV001023538, REVEL 0.34, AlphaMissense 0.12, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- T17N (p.Thr17Asn), rs138979875, ClinGen CA015929, ClinVar RCV000132258, ClinVar RCV000704459, REVEL 0.24, AlphaMissense 0.12, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- T17P (p.Thr17Pro), TOPMed rs1060503756, gnomAD rs1060503756, REVEL 0.30, CADD 3.84, Uncertain significance
- T17S (p.Thr17Ser), rs138979875, ClinGen CA338230688, ClinVar RCV003054582, AlphaMissense 0.12, MetaLR 0.81, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- L18F (p.Leu18Phe), rs2101551686, ClinGen CA338230679, ClinVar RCV001370070, ClinVar RCV004951632, REVEL 0.28, CADD 0.32, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- G19D (p.Gly19Asp), gnomAD rs1207765873, REVEL 0.51, CADD 20.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- G20R (p.Gly20Arg), rs1557749649, ClinGen CA338230656, ClinVar RCV001371998, ClinVar RCV002357269, REVEL 0.35, CADD 17.10, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A21D (p.Ala21Asp), rs2078163173, ClinGen CA338230637, ClinVar RCV004011812, ClinVar RCV006276449, AlphaMissense 0.07, MetaLR 0.85, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A21G (p.Ala21Gly), rs2078163173, ClinGen CA338230636, ClinVar RCV001993917, ClinVar RCV002361322, REVEL 0.41, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Gastrointestinal stro
- A21S (p.Ala21Ser), rs774266782, ClinGen CA338230638, ClinVar RCV003019444, AlphaMissense 0.09, MetaLR 0.82, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A21T (p.Ala21Thr), rs774266782, ClinGen CA089680, ClinVar RCV001321600, ExAC rs774266782, REVEL 0.37, AlphaMissense 0.09, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- A21V (p.Ala21Val), rs2078163173, ClinGen CA338230633, ClinVar RCV001929669, ClinVar RCV003225206, REVEL 0.37, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Pheochromocytoma
- C22F (p.Cys22Phe), rs141230910, ClinGen CA18612401, ClinVar RCV000541393, ClinVar RCV001101394, REVEL 0.38, CADD 22.30, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- C22S (p.Cys22Ser), rs141230910, ClinGen CA089705, ClinVar RCV000206152, ClinVar RCV000573095, REVEL 0.36, CADD 19.40, Conflicting interpretations, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- C22Y (p.Cys22Tyr), rs141230910, ClinGen CA089704, ClinVar RCV000633967, ClinVar RCV002377370, REVEL 0.40, CADD 22.40, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 4; Pheochromocytoma; Gastrointestinal st
- L23P (p.Leu23Pro), rs2525082834, ClinGen CA338230604, ClinVar RCV002701095, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- L23R (p.Leu23Arg), rs2525082838, ClinGen CA2582341894, ClinVar RCV003377776, Pathogenic
- L23V (p.Leu23Val), rs1553179319, ClinGen CA338230609, ClinVar RCV000519644, ClinVar RCV000633968, REVEL 0.36, CADD 19.30, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- Q24* (p.Gln24Ter), rs1570963430, ClinGen CA338230595, ClinVar RCV000823074, Ensembl rs1570963430, Pathogenic
- Q24E (p.Gln24Glu), rs1570963430, ClinGen CA338230593, ClinVar RCV004508373, ClinVar RCV006564832, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- Q24H (p.Gln24His), rs1553179312, ClinGen CA338230583, ClinVar RCV001053994, ClinVar RCV004000065, REVEL 0.39, CADD 32.00, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal stromal tumor; Pheoc
- Q24L (p.Gln24Leu), rs878854580, ClinGen CA338230586, ClinVar RCV002301421, ClinVar RCV003308107, AlphaMissense 0.07, MetaLR 0.83, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- Q24P (p.Gln24Pro), rs878854580, ClinGen CA10581754, ClinVar RCV000230020, ClinVar RCV003165627, AlphaMissense 0.07, MetaLR 0.83, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Gastrointestinal stromal
- Q24R (p.Gln24Arg), rs878854580, ClinGen CA338230587, ClinVar RCV001344511, ClinVar RCV002377462, AlphaMissense 0.07, MetaLR 0.83, Uncertain significance, not provided; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syn
- A25P (p.Ala25Pro), rs768101924, ClinGen CA089744, ClinVar RCV000555669, ClinVar RCV002384075, REVEL 0.66, CADD 22.90, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- A25S (p.Ala25Ser), rs768101924, ClinGen CA338228440, ClinVar RCV002002807, ClinVar RCV004804329, REVEL 0.45, CADD 21.20, Uncertain significance, Mitochondrial complex 2 deficiency, nuclear type 4; Gastrointestinal stromal tum
- A25T (p.Ala25Thr), rs768101924, ClinGen CA089743, ClinVar RCV000797417, ClinVar RCV001026392, REVEL 0.51, CADD 19.10, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- A25V (p.Ala25Val), NCI-TCGA Cosmic COSV6496, REVEL 0.38, CADD 18.70, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- S26F (p.Ser26Phe), rs2525060140, ClinGen CA338228412, ClinVar RCV002761526, ClinVar RCV006292250, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- S26P (p.Ser26Pro), Ensembl rs1570958165, REVEL 0.40, CADD 22.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- R27* (p.Arg27Ter), rs74315369, ClinGen CA016187, ClinVar RCV000013623, ClinVar RCV000129929, CADD 37.00, Pathogenic
- R27G (p.Arg27Gly), rs74315369, ClinGen CA016179, ClinVar RCV000148870, ClinVar RCV000408969, REVEL 0.61, CADD 22.00, Conflicting interpretations, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- R27P (p.Arg27Pro), rs373976827, ClinGen CA338228406, ClinVar RCV003803491, AlphaMissense 0.14, MetaLR 0.86, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- R27Q (p.Arg27Gln), rs373976827, ClinGen CA089772, ClinVar RCV000219487, ClinVar RCV000505281, REVEL 0.56, AlphaMissense 0.14, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- G28A (p.Gly28Ala), rs2101541615, ClinGen CA338228397, ClinVar RCV002434904, ClinVar RCV003776499, REVEL 0.36, AlphaMissense 0.07, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Pheochromocytoma; Pheochromocytom
- G28R (p.Gly28Arg), rs2078100857, ClinGen CA338228400, ClinVar RCV001242236, ClinVar RCV005480644, AlphaMissense 0.22, MetaLR 0.81, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- G28V (p.Gly28Val), rs2101541615, ClinGen CA338228395, ClinVar RCV003377771, AlphaMissense 0.07, MetaLR 0.78, Uncertain significance, Hereditary cancer-predisposing syndrome
- A29S (p.Ala29Ser), rs2525060090, ClinGen CA338228387, ClinVar RCV003791563, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- A29V (p.Ala29Val), NCI-TCGA Cosmic COSV1009, Ensembl rs2101541610, Variant assessed as somatic; moderate impact., in PPGL4
- Q30H (p.Gln30His), rs749662497, ClinGen CA338228363, NCI-TCGA Cosmic COSV6496, ClinVar RCV003781645, AlphaMissense 0.22, MetaLR 0.84, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- T31A (p.Thr31Ala), rs2525060053, ClinGen CA338228356, ClinVar RCV002304106, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- T31I (p.Thr31Ile), rs1553178750, ClinGen CA338228350, ClinVar RCV000537949, ClinVar RCV002377034, AlphaMissense 0.19, MetaLR 0.86, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- T31R (p.Thr31Arg), rs1553178750, ClinGen CA338228352, ClinVar RCV002295034, ClinVar RCV006287633, REVEL 0.54, AlphaMissense 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- A32G (p.Ala32Gly), Ensembl rs1570958135, Uncertain significance
- A32P (p.Ala32Pro), rs1570958136, ClinGen CA338228347, ClinVar RCV001970941, Ensembl rs1570958136, AlphaMissense 0.10, MetaLR 0.87, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- A32S (p.Ala32Ser), Ensembl rs1570958136, Uncertain significance
- A32T (p.Ala32Thr), rs1570958136, ClinGen CA338228349, ClinVar RCV001019432, ClinVar RCV002549504, AlphaMissense 0.10, MetaLR 0.87, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- A32V (p.Ala32Val), rs1570958135, ClinGen CA338228338, ClinVar RCV000822484, Ensembl rs1570958135, AlphaMissense 0.13, MetaLR 0.86, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- A33P (p.Ala33Pro), ExAC rs777898500, TOPMed rs777898500, gnomAD rs777898500, Likely benign
- A33T (p.Ala33Thr), rs777898500, ClinGen CA089777, ClinVar RCV001315755, ClinVar RCV002384398, REVEL 0.61, CADD 18.10, Conflicting interpretations, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- A33V (p.Ala33Val), rs1557746669, ClinGen CA338228321, NCI-TCGA Cosmic COSV6496, ClinVar RCV002846381, REVEL 0.46, CADD 22.60, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A34D (p.Ala34Asp), rs867908217, ClinGen CA338228314, ClinVar RCV001243759, TOPMed rs867908217, AlphaMissense 0.11, MetaLR 0.86, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- A34G (p.Ala34Gly), rs867908217, ClinGen CA338228313, ClinVar RCV001009717, ClinVar RCV003769421, REVEL 0.40, AlphaMissense 0.11, Uncertain significance, Gastrointestinal stromal tumor; Hereditary cancer-predisposing syndrome; Pheochr
- A34T (p.Ala34Thr), rs2078100708, ClinGen CA338228315, ClinVar RCV002435482, Ensembl rs2078100708, AlphaMissense 0.08, MetaLR 0.85, Uncertain significance, Hereditary cancer-predisposing syndrome
- A34V (p.Ala34Val), TOPMed rs867908217, gnomAD rs867908217, REVEL 0.41, AlphaMissense 0.11, Uncertain significance
- T35I (p.Thr35Ile), TOPMed rs1331420052, gnomAD rs1331420052, REVEL 0.33, CADD 11.70, Uncertain significance, Hereditary cancer-predisposing syndrome
- A36I (p.Ala36Ile), rs2078100640, ClinGen CA1139655478, ClinVar RCV001224016, ClinVar RCV002402697, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- A36S (p.Ala36Ser), rs1204932232, ClinGen CA338228304, ClinVar RCV000633956, ClinVar RCV004948490, REVEL 0.42, CADD 13.50, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 4; Pheochromocytoma; Gastrointestinal st
- A36T (p.Ala36Thr), rs1204932232, ClinGen CA338228306, ClinVar RCV002411034, gnomAD rs1204932232, REVEL 0.41, CADD 14.90, Uncertain significance, Hereditary cancer-predisposing syndrome
- A36V (p.Ala36Val), rs1337800267, ClinGen CA338228298, ClinVar RCV002424275, gnomAD rs1337800267, REVEL 0.37, CADD 22.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- P37A (p.Pro37Ala), rs761180960, ClinGen CA338228295, ClinVar RCV001899957, Ensembl rs761180960, AlphaMissense 0.11, MetaLR 0.83, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- P37L (p.Pro37Leu), TOPMed rs1324983452, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Gastrointestinal stro
- P37S (p.Pro37Ser), rs761180960, ClinGen CA18610390, ClinVar RCV001341003, ClinVar RCV004005169, REVEL 0.51, AlphaMissense 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- P37T (p.Pro37Thr), rs2101541552, ClinGen CA2573130758, ClinVar RCV002048011, Ensembl rs2101541552, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- R38C (p.Arg38Cys), rs202119350, ClinGen CA089513, ClinVar RCV000409187, ClinVar RCV000456572, REVEL 0.87, CADD 25.40, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Carney-Stratakis syndrome
- R38H (p.Arg38His), rs143058777, ClinGen CA089514, ClinVar RCV000230624, ClinVar RCV000260688, REVEL 0.51, CADD 23.70, Conflicting interpretations, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- R38P (p.Arg38Pro), rs143058777, ClinGen CA338228263, ClinVar RCV000817594, ClinVar RCV003307536, REVEL 0.57, CADD 23.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- I39V (p.Ile39Val), rs2525059890, ClinGen CA338228260, ClinVar RCV002985412, ClinVar RCV004065147, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- K40E (p.Lys40Glu), UniProt VAR 054375, REVEL 0.95, CADD 29.20, Pathogenic/Likely pathogenic, Inherited phaeochromocytoma and paraganglioma excluding NF1; Pheochromocytoma/pa
- K40N (p.Lys40Asn), rs1570958090, ClinGen CA338228226, ClinVar RCV000801303, ClinVar RCV002352362, AlphaMissense 0.99, MetaLR 0.98, Conflicting interpretations, Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal stromal tumor; Pheoc
- F42I (p.Phe42Ile), rs767667150, ClinGen CA338228194, ClinVar RCV002409688, AlphaMissense 0.98, MetaLR 0.91, Uncertain significance, Hereditary cancer-predisposing syndrome
- F42L (p.Phe42Leu), rs2101541516, ClinGen CA338228166, ClinVar RCV002015328, ClinVar RCV003303599, REVEL 0.90, AlphaMissense 0.98, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- F42S (p.Phe42Ser), rs2525059857, ClinGen CA338228190, ClinVar RCV002430319, ClinVar RCV003103490, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A43P (p.Ala43Pro), rs2078100395, ClinGen CA338228149, ClinVar RCV002376483, ClinVar RCV003094846, AlphaMissense 0.08, MetaLR 0.75, Likely pathogenic, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A43S (p.Ala43Ser), rs2078100395, ClinGen CA338228147, ClinVar RCV001213509, Ensembl rs2078100395, AlphaMissense 0.08, MetaLR 0.75, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- A43T (p.Ala43Thr), rs2078100395, ClinGen CA338228161, ClinVar RCV002872245, REVEL 0.42, AlphaMissense 0.08, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- A43V (p.Ala43Val), rs2078100382, ClinGen CA338228143, ClinVar RCV003812260, ClinVar RCV004006075, AlphaMissense 0.18, MetaLR 0.89, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- I44F (p.Ile44Phe), rs200418115, ClinGen CA338228141, ClinVar RCV004455303, ClinVar RCV006564764, AlphaMissense 0.07, MetaLR 0.88, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- I44M (p.Ile44Met), Ensembl rs2078100339, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- I44T (p.Ile44Thr), rs2525059821, ClinGen CA338228137, ClinVar RCV003176555, ClinVar RCV006561126, Conflicting interpretations, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- I44V (p.Ile44Val), rs200418115, ClinGen CA089518, ClinVar RCV000521448, ClinVar RCV000693783, REVEL 0.44, AlphaMissense 0.07, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- Y45* (p.Tyr45Ter), rs1351034939, ClinGen CA338228102, ClinVar RCV001242731, gnomAD rs1351034939, Pathogenic
- Y45C (p.Tyr45Cys), rs2525059811, ClinGen CA338228108, ClinVar RCV002695264, ClinVar RCV005724827, REVEL 0.92, CADD 30.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- R46* (p.Arg46Ter), rs74315370, ClinGen CA015507, NCI-TCGA Cosmic COSV6496, ClinVar RCV000132150, AlphaMissense 0.99, MetaLR 0.99, Pathogenic, in PPGL4
- R46G (p.Arg46Gly), rs74315370, ClinGen CA015497, ClinVar RCV000216404, ClinVar RCV000800486, AlphaMissense 0.99, MetaLR 0.99, Pathogenic, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- R46L (p.Arg46Leu), rs772551056, ClinGen CA16609944, ClinVar RCV000473045, ClinVar RCV000571526, REVEL 0.93, CADD 29.40, Pathogenic/Likely pathogenic, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- R46Q (p.Arg46Gln), rs772551056, ClinGen CA015517, ClinVar RCV000162578, ClinVar RCV000183217, REVEL 0.91, CADD 29.50, Pathogenic/Likely pathogenic, SDHB-related disorder; Mitochondrial complex 2 deficiency, nuclear type 4; Gastr
- W47* (p.Trp47Ter), gnomAD rs1163621416, CADD 41.00, Pathogenic
- W47R (p.Trp47Arg), rs2525059756, ClinGen CA338228089, ClinVar RCV002389222, ClinVar RCV005227720, REVEL 0.95, CADD 29.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Pheochromocytoma/para
- W47S (p.Trp47Ser), rs1163621416, ClinGen CA338228071, ClinVar RCV003296709, ClinVar RCV004009703, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- D48N (p.Asp48Asn), rs2078100198, ClinGen CA338228044, ClinVar RCV001049021, Ensembl rs2078100198, AlphaMissense 0.12, MetaLR 0.81, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal stromal tumor; Pheoc
- D48V (p.Asp48Val), rs202101384, ClinGen CA015528, ClinVar RCV000032784, ClinVar RCV000470589, REVEL 0.92, CADD 29.70, Conflicting interpretations, Mitochondrial complex 2 deficiency, nuclear type 4; Hereditary cancer-predisposi
- P49L (p.Pro49Leu), rs2078100131, ClinGen CA338228009, ClinVar RCV001234532, ClinVar RCV004004854, AlphaMissense 0.65, MetaLR 0.98, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- P49Q (p.Pro49Gln), rs2078100131, ClinGen CA338228018, ClinVar RCV003801638, Ensembl rs2078100131, AlphaMissense 0.65, MetaLR 0.98, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- P49S (p.Pro49Ser), rs2078100145, ClinGen CA338228020, ClinVar RCV003794629, ClinVar RCV004950688, REVEL 0.83, CADD 27.90, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- D50E (p.Asp50Glu), rs1570958024, ClinGen CA338227986, ClinVar RCV000797389, ClinVar RCV002388451, REVEL 0.43, CADD 17.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- D50G (p.Asp50Gly), TOPMed rs201219456
- D50H (p.Asp50His), rs1060503765, ClinGen CA16609947, ClinVar RCV000468197, ClinVar RCV004002004, REVEL 0.81, AlphaMissense 0.14, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- D50N (p.Asp50Asn), rs1060503765, ClinGen CA338228001, ClinVar RCV001229478, ClinVar RCV001819929, AlphaMissense 0.14, MetaLR 0.93, Uncertain significance, not specified; Gastrointestinal stromal tumor; Pheochromocytoma
- D50Y (p.Asp50Tyr), rs1060503765, ClinGen CA338227992, ClinVar RCV003176554, ClinVar RCV003778954, AlphaMissense 0.14, MetaLR 0.93, Uncertain significance, Pheochromocytoma; Pheochromocytoma/paraganglioma syndrome 4; Gastrointestinal st
- K51N (p.Lys51Asn), Ensembl rs2078100060
- K51T (p.Lys51Thr), rs2101541430, ClinGen CA338227977, ClinVar RCV001945934, Ensembl rs2101541430, AlphaMissense 0.11, MetaLR 0.86, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- A52D (p.Ala52Asp), rs878854573, ClinGen CA10581751, ClinVar RCV000234165, gnomAD rs878854573, AlphaMissense 0.09, MetaLR 0.87, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- A52P (p.Ala52Pro), TOPMed rs1183722041, gnomAD rs1183722041, REVEL 0.28, AlphaMissense 0.07
- A52S (p.Ala52Ser), rs1183722041, ClinGen CA338227954, ClinVar RCV003815450, AlphaMissense 0.07, MetaLR 0.82, Uncertain significance, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
- A52T (p.Ala52Thr), TOPMed rs1183722041, gnomAD rs1183722041
- A52V (p.Ala52Val), rs878854573, ClinGen CA338227952, ClinVar RCV002405376, gnomAD rs878854573, REVEL 0.34, AlphaMissense 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome
- G53E (p.Gly53Glu), rs34916635, ClinGen CA015535, ClinVar RCV000163315, ClinVar RCV000266464, REVEL 0.61, CADD 22.40, Benign/Likely benign, Mitochondrial complex 2 deficiency, nuclear type 4; Gastrointestinal stromal tum
- G53R (p.Gly53Arg), rs1570958009, ClinGen CA338227946, ClinVar RCV001012281, ClinVar RCV005394625, REVEL 0.71, CADD 24.60, Uncertain significance, Mitochondrial complex 2 deficiency, nuclear type 4; Carney-Stratakis syndrome; P
- D54N (p.Asp54Asn), rs1570957997, ClinGen CA338227932, ClinVar RCV001012407, ClinVar RCV001860707, AlphaMissense 0.12, MetaLR 0.87, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- D54V (p.Asp54Val), rs1553178735, ClinGen CA338227918, ClinVar RCV000559773, ClinVar RCV003380602, AlphaMissense 0.14, MetaLR 0.88, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma; Pheochromocytoma/paraganglioma
- D54Y (p.Asp54Tyr), Ensembl rs1570957997, Uncertain significance
- K55R (p.Lys55Arg), rs764843485, ClinGen CA089520, ClinVar RCV000707718, ClinVar RCV002397494, REVEL 0.64, CADD 24.20, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheoc
- K55T (p.Lys55Thr), rs764843485, ClinGen CA338227887, ClinVar RCV004508358, ExAC rs764843485, REVEL 0.84, CADD 27.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- P56A (p.Pro56Ala), rs2525059578, ClinGen CA338227861, ClinVar RCV002403968, Uncertain significance, Hereditary cancer-predisposing syndrome
- P56H (p.Pro56His), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- P56L (p.Pro56Leu), rs2525059575, ClinGen CA338227843, ClinVar RCV004508359, Uncertain significance, Hereditary cancer-predisposing syndrome
- P56R (p.Pro56Arg), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- H57R (p.His57Arg), rs35962811, ClinGen CA015557, ClinVar RCV000122000, ClinVar RCV000129655, REVEL 0.55, CADD 0.29, Benign/Likely benign, Pheochromocytoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma
Public SDHB analysis runs
- SDHB analysis run — SDHB (925 variants) — completed 2026-08-18