SDHC (Q99643) variants and mutations
SDHC (also known as Q99643) is a human protein-coding gene encoding a succinate dehydrogenase cytochrome b560 subunit, mitochondrial protein. It anchors succinate dehydrogenase to the inner mitochondrial membrane and helps transfer electrons from the catalytic subunits to ubiquinone. Heterozygous loss-of-function variants predispose to paraganglioma, pheochromocytoma, and some gastrointestinal stromal tumors. This analysis covers 515 SDHC variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes hereditary pheochromocytoma-paraganglioma, Carney-Stratakis syndrome, and pheochromocytoma/paraganglioma syndrome 3. Example SDHC variants include M1I, M1L, and M1R.
Variant analysis overview
- Gene: SDHC
- Protein: Q99643
- UniProt accession: Q99643
- Organism: Homo sapiens
- Variants analyzed: 515
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 466 unspecified-consequence records; 25 synonymous variants; 18 missense variants; 4 frameshift variants; 1 in-frame deletions; 1 splice-region variants; 1 substitution
- Prediction scores: 407 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hereditary pheochromocytoma-paraganglioma, Carney-Stratakis syndrome, pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor, hereditary neoplastic syndrome, Inherited cancer-predisposing syndrome, neurodegenerative disease, paraganglioma, Cowden disease, lung carcinoma, breast lobular carcinoma, malignant endocrine neoplasm.
Protein structure and variant hotspots
- Protein features: 3 transmembrane segments; 1 binding sites.
- Structural context: 212 variants have structural context.
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 SDHC variants
Examples include M1I, M1L, M1R, M1T, M1V, A2G, A2P, A2T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs587776652, ClinGen CA016312, ClinVar RCV000007663, ClinVar RCV000812224, MetaLR 0.92, MetaSVM 1.07, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; not p
- M1L (p.Met1Leu), rs755235380, ClinGen CA343354884, ClinVar RCV002933132, ClinGen CA343354875, MetaLR 0.90, MetaSVM 1.03, Pathogenic, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- M1R (p.Met1Arg), rs1670517782, ClinGen CA343354891, ClinVar RCV001244070, ClinVar RCV005245801, MetaLR 0.92, MetaSVM 1.08, Pathogenic, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; not p
- M1T (p.Met1Thr), rs1670517782, ClinGen CA343354890, ClinVar RCV003800158, MetaLR 0.92, MetaSVM 1.08, Pathogenic, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- M1V (p.Met1Val), rs755235380, ClinGen CA046289, ClinVar RCV000467345, ClinVar RCV000492170, MetaLR 0.90, MetaSVM 1.03, Pathogenic, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A2G (p.Ala2Gly), rs781337432, ClinGen CA048106, ClinVar RCV000821924, ClinVar RCV003307554, REVEL 0.39, MetaLR 0.87, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- A2P (p.Ala2Pro), rs1198315342, ClinGen CA343354901, ClinVar RCV001056965, ClinVar RCV005049749, REVEL 0.62, AlphaMissense 0.29, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Carne
- A2T (p.Ala2Thr), rs1198315342, ClinGen CA343354908, ClinVar RCV000542616, ClinVar RCV003159828, AlphaMissense 0.29, MetaLR 0.90, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A2V (p.Ala2Val), rs781337432, ClinGen CA343354918, ClinVar RCV003387391, ClinVar RCV003778141, REVEL 0.64, MetaLR 0.90, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A2A (p.Ala2Ala), rs775353334, gnomAD 1-161314411-T-G, CADD 13.20
- A3E (p.Ala3Glu), rs142139022, ClinGen CA343354948, ClinVar RCV001222737, ClinVar RCV002256707, REVEL 0.59, MetaLR 0.89, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- A3P (p.Ala3Pro), rs748243732, ClinGen CA343354942, ClinVar RCV003801143, ClinVar RCV004661781, REVEL 0.61, MetaLR 0.91, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor; Hered
- A3R (p.Ala3Arg), rs786205146, ClinGen CA016383, ClinVar RCV000170331, ClinVar RCV000492519, Pathogenic
- A3S (p.Ala3Ser), rs748243732, ClinGen CA048618, cosmic curated COSV10967, ClinVar RCV000472430, REVEL 0.41, MetaLR 0.88, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A3T (p.Ala3Thr), rs748243732, ClinGen CA048607, cosmic curated COSV60669, ClinVar RCV000462901, REVEL 0.47, MetaLR 0.89, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A3V (p.Ala3Val), rs142139022, ClinGen CA011497, cosmic curated COSV60668, ClinVar RCV000148872, REVEL 0.61, MetaLR 0.79, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A3A (p.Ala3Ala), rs749265569, gnomAD 1-161314414-G-A, CADD 13.90
- L4M (p.Leu4Met), ExAC rs770796603, gnomAD rs770796603, Likely benign
- L4P (p.Leu4Pro), rs774299337, ClinGen CA045713, ClinVar RCV000411462, ClinVar RCV000547937, REVEL 0.72, AlphaMissense 0.22, Uncertain significance, not provided; Gastrointestinal stromal tumor; Hereditary cancer-predisposing syn
- L4Q (p.Leu4Gln), rs774299337, ClinGen CA343354963, ClinVar RCV002295767, AlphaMissense 0.22, MetaLR 0.86, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- L4R (p.Leu4Arg), rs774299337, ClinGen CA343354967, ClinVar RCV001241983, ExAC rs774299337, AlphaMissense 0.22, MetaLR 0.86, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- L4V (p.Leu4Val), rs770796603, ClinGen CA343354959, ClinVar RCV000641905, ExAC rs770796603, AlphaMissense 0.08, MetaLR 0.65, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- L4L (p.Leu4Leu), rs770796603, gnomAD 1-161314415-C-T, AlphaMissense 0.08, MetaLR 0.65
- L5F (p.Leu5Phe), rs771746264, ClinGen CA016220, ClinVar RCV000163869, ClinVar RCV000367287, REVEL 0.43, MetaLR 0.80, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- L5M (p.Leu5Met), rs894925936, ClinGen CA31675345, cosmic curated COSV10648, ClinVar RCV000821325, REVEL 0.51, MetaLR 0.84, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Gastrointestinal stromal
- L5S (p.Leu5Ser), rs1277411736, ClinGen CA343354988, ClinVar RCV000700226, ClinVar RCV001597205, REVEL 0.70, MetaLR 0.79, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- L5L (p.Leu5Leu), rs771746264, gnomAD 1-161314420-G-A, CADD 11.40
- L6=, NCI-TCGA Cosmic COSV6066, Variant assessed as somatic; low impact.
- L6M (p.Leu6Met), TOPMed rs1325823872, MetaLR 0.90, MetaSVM 0.60, Uncertain significance
- L6P (p.Leu6Pro), rs1211574644, ClinGen CA343355011, ClinVar RCV001060877, ClinVar RCV004659325, REVEL 0.79, MetaLR 0.91, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- L6V (p.Leu6Val), rs1325823872, ClinGen CA343355002, ClinVar RCV001216251, ClinVar RCV004803572, REVEL 0.47, MetaLR 0.87, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- L6L (p.Leu6Leu), rs1325823872, gnomAD 1-161314421-C-T, CADD 14.20
- R7* (p.Arg7Ter), rs1553260596, ClinGen CA658822732, ClinVar RCV000657830, ClinVar RCV003767891, Pathogenic
- R7=, NCI-TCGA Cosmic COSV6066, cosmic curated COSV60667, TOPMed rs1670521233, Uncertain significance
- R7G (p.Arg7Gly), TOPMed rs1670521233, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- R7K (p.Arg7Lys), rs2102271857, ClinGen CA343355022, ClinVar RCV002044863, ClinVar RCV004656677, AlphaMissense 0.45, MetaLR 0.79, Likely pathogenic, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor; Hered
- H8N (p.His8Asn), rs746666691, ClinGen CA046587, ClinVar RCV002045911, ClinVar RCV002458994, REVEL 0.30, AlphaMissense 0.08, Uncertain significance, not provided; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syn
- H8Q (p.His8Gln), rs761381438, ClinGen CA047351, ClinVar RCV000543957, ClinVar RCV001015761, REVEL 0.43, MetaLR 0.81, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- H8R (p.His8Arg), rs776123707, ClinGen CA046629, ClinVar RCV001346280, ClinVar RCV002447417, REVEL 0.29, MetaLR 0.75, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- H8Y (p.His8Tyr), rs746666691, ClinGen CA046597, ClinVar RCV000555154, ClinVar RCV003302832, AlphaMissense 0.08, MetaLR 0.78, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- H8H (p.His8His), rs761381438, gnomAD 1-161323617-C-T, CADD 1.87
- V9F (p.Val9Phe), rs774768866, ClinGen CA343359289, cosmic curated COSV61370, ClinVar RCV001207219, REVEL 0.48, AlphaMissense 0.09, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- V9I (p.Val9Ile), rs774768866, ClinGen CA047404, cosmic curated COSV61368, ClinVar RCV000234613, REVEL 0.17, AlphaMissense 0.09, Uncertain significance, not specified; Hereditary cancer-predisposing syndrome; Hereditary pheochromocyt
- V9L (p.Val9Leu), rs774768866, ClinGen CA343359286, ClinVar RCV004508383, AlphaMissense 0.09, MetaLR 0.53, Uncertain significance, Hereditary cancer-predisposing syndrome
- V9V (p.Val9Val), gnomAD 1-161323620-T-C, CADD 6.78
- G10A (p.Gly10Ala), rs1670923061, ClinGen CA343359309, ClinVar RCV001308663, ClinVar RCV003313212, AlphaMissense 0.13, MetaLR 0.79, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; not p
- G10D (p.Gly10Asp), gnomAD 1-161323622-G-A, REVEL 0.76, MetaLR 0.90
- G10G (p.Gly10Gly), rs1170595036, gnomAD 1-161323623-T-C, CADD 6.70
- R11C (p.Arg11Cys), rs759914119, ClinGen CA047542, ClinVar RCV000700704, ClinVar RCV002268262, REVEL 0.78, MetaLR 0.91, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; not specified; Hereditary cancer
- R11H (p.Arg11His), rs767802663, ClinGen CA047588, ClinVar RCV000233939, ClinVar RCV001762528, REVEL 0.52, MetaLR 0.85, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- R11L (p.Arg11Leu), rs767802663, ClinGen CA011533, ClinVar RCV000167052, ClinVar RCV000477280, REVEL 0.79, MetaLR 0.87, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- R11S (p.Arg11Ser), ExAC rs759914119, TOPMed rs759914119, gnomAD rs759914119, REVEL 0.79, MetaLR 0.91, Uncertain significance
- H12D (p.His12Asp), rs1670923808, ClinGen CA343359332, ClinVar RCV001299212, ClinVar RCV003373104, REVEL 0.65, MetaLR 0.83, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- H12L (p.His12Leu), rs1670923933, ClinGen CA343359345, ClinVar RCV002751546, AlphaMissense 0.07, MetaLR 0.76, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- H12R (p.His12Arg), rs1670923933, ClinGen CA343359348, ClinVar RCV001208768, Ensembl rs1670923933, AlphaMissense 0.07, MetaLR 0.76, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- H12Y (p.His12Tyr), gnomAD 1-161323627-C-T, REVEL 0.44, MetaLR 0.72
- H12H (p.His12His), gnomAD 1-161323629-T-C, CADD 0.60
- C13F (p.Cys13Phe), rs1558164528, ClinGen CA343359375, ClinVar RCV000694826, Ensembl rs1558164528, REVEL 0.85, AlphaMissense 0.09, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- C13R (p.Cys13Arg), rs2526332513, ClinGen CA343359362, ClinVar RCV003813489, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- C13S (p.Cys13Ser), rs2526332513, ClinGen CA343359358, ClinVar RCV003807375, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- C13Y (p.Cys13Tyr), rs1558164528, ClinGen CA343359369, ClinVar RCV001230946, Ensembl rs1558164528, AlphaMissense 0.09, MetaLR 0.88, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- L14F (p.Leu14Phe), rs760986608, ClinGen CA047926, ClinVar RCV000506825, ClinVar RCV000535370, REVEL 0.71, MetaLR 0.93, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- L14V (p.Leu14Val), gnomAD 1-161323633-C-G, REVEL 0.68, MetaLR 0.90
- L14L (p.Leu14Leu), rs1331533952, gnomAD 1-161323635-C-T, CADD 4.64
- R15* (p.Arg15Ter), rs201286421, ClinGen CA011542, NCI-TCGA Cosmic COSV6136, cosmic curated COSV61368, AlphaMissense 0.12, MetaLR 0.84, Pathogenic
- R15G (p.Arg15Gly), rs201286421, ClinGen CA343359413, ClinVar RCV001875430, ClinVar RCV002473317, AlphaMissense 0.12, MetaLR 0.84, Uncertain significance, not provided; Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stroma
- R15Q (p.Arg15Gln), rs1294873008, ClinGen CA343359420, ClinVar RCV000811379, ClinVar RCV001022590, REVEL 0.36, MetaLR 0.64, Uncertain significance, Gastrointestinal stromal tumor; Hereditary pheochromocytoma and paraganglioma; P
- A16D (p.Ala16Asp), rs1558164567, ClinGen CA343359442, ClinVar RCV000697414, gnomAD rs1558164567, REVEL 0.66, MetaLR 0.72, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- A16T (p.Ala16Thr), rs878994954, ClinGen CA31683716, ClinVar RCV000821024, ClinVar RCV002332706, REVEL 0.21, MetaLR 0.53, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Gastrointestinal stromal
- A16V (p.Ala16Val), rs1558164567, ClinGen CA343359448, ClinVar RCV000699024, ClinVar RCV003472228, REVEL 0.47, MetaLR 0.70, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A16A (p.Ala16Ala), rs1553261765, gnomAD 1-161323641-C-G, CADD 6.21
- H17L (p.His17Leu), rs1571843720, ClinGen CA343359471, ClinVar RCV001023536, Ensembl rs1571843720, AlphaMissense 0.11, MetaLR 0.75, Uncertain significance, Hereditary cancer-predisposing syndrome
- H17Q (p.His17Gln), rs1571843732, ClinGen CA343359474, ClinVar RCV001023707, ClinVar RCV005213444, AlphaMissense 0.11, MetaLR 0.77, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor; Hered
- H17R (p.His17Arg), rs1571843720, ClinGen CA343359467, ClinVar RCV004508389, REVEL 0.41, AlphaMissense 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- H17Y (p.His17Tyr), rs2102295552, ClinGen CA343359452, ClinVar RCV001372274, Ensembl rs2102295552, AlphaMissense 0.09, MetaLR 0.71, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- F18L (p.Phe18Leu), rs200761743, ClinGen CA048079, ClinVar RCV000223312, ClinVar RCV000552969, REVEL 0.26, MetaLR 0.16, Conflicting interpretations, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- F18V (p.Phe18Val), gnomAD rs1341059786, REVEL 0.20, MetaLR 0.51
- F18Y (p.Phe18Tyr), gnomAD rs1228455705, REVEL 0.34, MetaLR 0.61
- F18* (p.Phe18Ter), gnomAD 1-161323644-CTT-C, CADD 24.40
- F18I (p.Phe18Ile), gnomAD 1-161323645-T-A, REVEL 0.18, MetaLR 0.46
- S19G (p.Ser19Gly), rs1670926798, ClinGen CA343359514, ClinVar RCV001318927, Ensembl rs1670926798, AlphaMissense 0.09, MetaLR 0.47, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- S19I (p.Ser19Ile), rs2526332789, ClinGen CA343359527, ClinVar RCV003225472, Uncertain significance, not provided
- S19R (p.Ser19Arg), gnomAD rs1354846104, MetaLR 0.70, MetaSVM 0.27
- P20A (p.Pro20Ala), rs757465324, ClinGen CA343359540, ClinVar RCV003305382, AlphaMissense 0.08, MetaLR 0.58, Uncertain significance, Hereditary cancer-predisposing syndrome
- P20R (p.Pro20Arg), rs2102295625, ClinGen CA343359546, ClinVar RCV001763998, ClinVar RCV003298982, AlphaMissense 0.07, MetaLR 0.88, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- P20S (p.Pro20Ser), rs757465324, ClinGen CA048093, ClinVar RCV003201458, ClinVar RCV003779736, REVEL 0.26, AlphaMissense 0.08, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- P20P (p.Pro20Pro), gnomAD 1-161323653-T-C, CADD 12.00
- Q21* (p.Gln21Ter), rs1553261768, ClinGen CA343359555, ClinVar RCV003802140, TOPMed rs1553261768, CADD 43.00, Pathogenic
- Q21E (p.Gln21Glu), rs1553261768, ClinGen CA343359552, ClinVar RCV000560999, ClinVar RCV000641909, REVEL 0.34, MetaLR 0.72, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- Q21H (p.Gln21His), rs1670927628, ClinGen CA343359564, ClinVar RCV004508391, ClinVar RCV005216222, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- Q21L (p.Gln21Leu), rs1670927465, ClinGen CA343359558, ClinVar RCV004508390, AlphaMissense 0.07, MetaLR 0.43, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q21R (p.Gln21Arg), Ensembl rs1670927465, REVEL 0.24, AlphaMissense 0.07
- Q21Q (p.Gln21Gln), rs1670927628, gnomAD 1-161323656-G-A, CADD 7.88
- L22F (p.Leu22Phe), rs1473438869, ClinGen CA343359574, ClinVar RCV000526806, ClinVar RCV000663232, REVEL 0.49, MetaLR 0.89, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- C23R (p.Cys23Arg), rs2102295690, ClinGen CA343359589, ClinVar RCV001975378, Ensembl rs2102295690, REVEL 0.65, MetaLR 0.85, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- C23Y (p.Cys23Tyr), rs2526333046, ClinGen CA343359599, ClinVar RCV003380143, ClinVar RCV003778129, REVEL 0.34, MetaLR 0.83, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- I24N (p.Ile24Asn), rs2102295698, ClinGen CA343359616, ClinVar RCV001999496, Ensembl rs2102295698, AlphaMissense 0.18, MetaLR 0.79, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- I24I (p.Ile24Ile), gnomAD 1-161323665-C-A, CADD 12.10
- R25G (p.Arg25Gly), rs878854587, ClinGen CA10581735, ClinVar RCV000229192, ClinVar RCV002378989, REVEL 0.89, MetaLR 0.89, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- R25I (p.Arg25Ile), rs2526333111, ClinGen CA343359636, ClinVar RCV003104850, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- R25K (p.Arg25Lys), gnomAD 1-161323667-G-A, REVEL 0.70, MetaLR 0.90
- R25T (p.Arg25Thr), gnomAD 1-161323667-G-C, REVEL 0.79, MetaLR 0.92
- N26D (p.Asn26Asp), rs1670928309, ClinGen CA343359648, ClinVar RCV001202058, ClinVar RCV002402574, AlphaMissense 0.13, MetaLR 0.80, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- N26S (p.Asn26Ser), rs1670928456, ClinGen CA343359655, ClinVar RCV001338813, Ensembl rs1670928456, AlphaMissense 0.09, MetaLR 0.78, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- N26K (p.Asn26Lys), gnomAD 1-161328396-T-A, REVEL 0.34, MetaLR 0.72
- A27T (p.Ala27Thr), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- A27V (p.Ala27Val), rs2102307553, ClinGen CA343360823, ClinVar RCV003808032, Ensembl rs2102307553, AlphaMissense 0.11, MetaLR 0.72, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- A27D (p.Ala27Asp), gnomAD 1-161328398-C-A, REVEL 0.75, MetaLR 0.90
- A27A (p.Ala27Ala), rs876659297, gnomAD 1-161328399-T-C, CADD 13.60
- V28F (p.Val28Phe), rs754818119, ClinGen CA048634, ClinVar RCV000707254, ClinVar RCV001258164, REVEL 0.57, AlphaMissense 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- V28I (p.Val28Ile), rs754818119, ClinGen CA343360829, ClinVar RCV000793631, ClinVar RCV002424797, REVEL 0.22, AlphaMissense 0.13, Uncertain significance, not specified; Hereditary cancer-predisposing syndrome; Hereditary pheochromocyt
- V28L (p.Val28Leu), rs754818119, ClinGen CA343360831, ClinVar RCV001208039, ClinVar RCV002509630, AlphaMissense 0.13, MetaLR 0.69, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; not p
- P29A (p.Pro29Ala), rs878854588, ClinGen CA10581736, ClinVar RCV000233108, ClinVar RCV001018077, REVEL 0.67, MetaLR 0.92, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- P29L (p.Pro29Leu), rs1671145169, ClinGen CA343360854, cosmic curated COSV61368, ClinVar RCV001208446, REVEL 0.73, MetaLR 0.90, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- P29S (p.Pro29Ser), NCI-TCGA Cosmic COSV6136, cosmic curated COSV61369, MetaLR 0.90, MetaSVM 0.92, Uncertain significance, Hereditary cancer-predisposing syndrome
- P29T (p.Pro29Thr), gnomAD 1-161328403-C-A, REVEL 0.71, MetaLR 0.90
- L30L (p.Leu30Leu), rs780791443, gnomAD 1-161328408-G-A, CADD 14.50
- G31* (p.Gly31Ter), Ensembl rs2102307595
- G31R (p.Gly31Arg), rs2102307595, ClinGen CA343360878, ClinVar RCV002302137, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- T32A (p.Thr32Ala), rs1457574786, ClinGen CA343360898, ClinVar RCV000530558, ClinVar RCV003302833, REVEL 0.63, MetaLR 0.91, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- T32N (p.Thr32Asn), rs1571851464, ClinGen CA343360901, ClinVar RCV001019542, ClinVar RCV001204950, REVEL 0.61, AlphaMissense 0.14, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- T32S (p.Thr32Ser), rs1571851464, ClinGen CA343360903, ClinVar RCV001359750, Ensembl rs1571851464, AlphaMissense 0.14, MetaLR 0.92, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- T33A (p.Thr33Ala), rs747828462, ClinGen CA048686, ClinVar RCV001240362, ClinVar RCV003166499, REVEL 0.53, MetaLR 0.85, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- T33K (p.Thr33Lys), rs148566767, ClinGen CA343360915, cosmic curated COSV10441, ClinVar RCV001063469, AlphaMissense 0.23, MetaLR 0.92, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; not p
- T33M (p.Thr33Met), rs148566767, ClinGen CA048701, NCI-TCGA Cosmic COSV1044, ClinVar RCV000459835, REVEL 0.56, AlphaMissense 0.23, Conflicting interpretations, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- T33del (p.Thr33del), gnomAD 1-161328411-AACC-, CADD 21.20
- T33R (p.Thr33Arg), gnomAD 1-161328416-C-G, REVEL 0.71, MetaLR 0.92
- T33T (p.Thr33Thr), gnomAD 1-161328417-G-C, CADD 9.65
- A34R (p.Ala34Arg), rs2526364101, ClinGen CA2580061309, ClinVar RCV002376670, ClinVar RCV005248682, Pathogenic
- A34T (p.Ala34Thr), NCI-TCGA Cosmic COSV6136, cosmic curated COSV61367, Ensembl rs1671146418, MetaLR 0.95, MetaSVM 1.08, Variant assessed as somatic; moderate impact.
- A34A (p.Ala34Ala), gnomAD 1-161328420-C-G, CADD 11.30
- K35E (p.Lys35Glu), rs746315913, ClinGen CA045660, ClinVar RCV001017121, ClinVar RCV001035296, REVEL 0.56, MetaLR 0.88, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; not provided; Pheochromocytoma/pa
- K35N (p.Lys35Asn), rs2526364324, ClinGen CA343360956, ClinVar RCV003806081, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- K35R (p.Lys35Arg), rs1342764291, ClinGen CA343360950, ClinVar RCV001017124, ClinVar RCV005423786, AlphaMissense 0.28, MetaLR 0.91, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- K35T (p.Lys35Thr), rs1342764291, ClinGen CA343360949, ClinVar RCV001322510, gnomAD rs1342764291, AlphaMissense 0.28, MetaLR 0.91, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- K35K (p.Lys35Lys), gnomAD 1-161328423-A-G, CADD 11.00
- E36K (p.Glu36Lys), rs2526364346, ClinGen CA343360966, ClinVar RCV003806932, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- E36D (p.Glu36Asp), gnomAD 1-161328426-A-C, REVEL 0.55, MetaLR 0.85
- E37G (p.Glu37Gly), rs1671147192, ClinGen CA343360993, ClinVar RCV003045586, AlphaMissense 0.78, MetaLR 0.95, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- E37K (p.Glu37Lys), TOPMed rs1671147063, MetaLR 0.93, MetaSVM 1.01, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- E37V (p.Glu37Val), rs1671147192, ClinGen CA343360995, ClinVar RCV001344166, ClinVar RCV002438791, REVEL 0.82, AlphaMissense 0.78, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- E37E (p.Glu37Glu), gnomAD 1-161328429-G-A, CADD 9.71
- M38I (p.Met38Ile), rs868556406, ClinGen CA31686019, ClinVar RCV000641915, ClinVar RCV002458062, REVEL 0.69, MetaLR 0.93, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; not p
- M38T (p.Met38Thr), rs1671147353, ClinGen CA343361013, ClinVar RCV001247507, Ensembl rs1671147353, AlphaMissense 0.75, MetaLR 0.92, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- E39* (p.Glu39Ter), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, Variant assessed as somatic; high impact.
- E39A (p.Glu39Ala), rs1060501388, ClinGen CA16609909, ClinVar RCV000456335, ClinVar RCV002256262, REVEL 0.37, AlphaMissense 0.14, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- E39G (p.Glu39Gly), rs1060501388, ClinGen CA343361032, ClinVar RCV002329834, ClinVar RCV004572276, AlphaMissense 0.14, MetaLR 0.68, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- E39Q (p.Glu39Gln), rs2526364595, ClinGen CA343361026, ClinVar RCV003800154, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- R40G (p.Arg40Gly), rs978019587, ClinGen CA343361043, ClinVar RCV000695000, TOPMed rs978019587, AlphaMissense 0.18, MetaLR 0.84, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- R40L (p.Arg40Leu), ExAC rs772450693, TOPMed rs772450693, gnomAD rs772450693, REVEL 0.46, MetaLR 0.70, Uncertain significance
- R40Q (p.Arg40Gln), rs772450693, ClinGen CA045699, ClinVar RCV000226923, ClinVar RCV000568226, REVEL 0.25, MetaLR 0.50, Conflicting interpretations, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- R40W (p.Arg40Trp), rs978019587, ClinGen CA31686023, cosmic curated COSV61368, ClinVar RCV000641916, REVEL 0.43, AlphaMissense 0.18, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; not p
- R40R (p.Arg40Arg), gnomAD 1-161328436-C-A, CADD 13.00
- F41I (p.Phe41Ile), Ensembl rs2102307780, Uncertain significance
- F41L (p.Phe41Leu), rs2102307780, NCI-TCGA TCGA novel, ClinGen CA343361055, ClinVar RCV001960802, AlphaMissense 0.99, MetaLR 0.93, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- F41S (p.Phe41Ser), rs1671152402, ClinGen CA343361060, ClinVar RCV001056822, ClinVar RCV003307883, AlphaMissense 0.95, MetaLR 0.93, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- W42R (p.Trp42Arg), gnomAD 1-161328442-T-C, REVEL 0.87, MetaLR 0.97
- N43H (p.Asn43His), rs1553262439, ClinGen CA343361095, ClinVar RCV000641914, ClinVar RCV001800837, REVEL 0.42, MetaLR 0.86, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- N43I (p.Asn43Ile), rs747349777, ClinGen CA343361108, ClinVar RCV002383269, AlphaMissense 0.09, MetaLR 0.55, Uncertain significance, Hereditary cancer-predisposing syndrome
- N43S (p.Asn43Ser), rs747349777, ClinGen CA045754, ClinVar RCV000233052, ClinVar RCV000763756, REVEL 0.22, AlphaMissense 0.09, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- K44E (p.Lys44Glu), rs2102307825, ClinGen CA343361123, ClinVar RCV002043605, ClinVar RCV005724737, AlphaMissense 0.49, MetaLR 0.93, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3; Hered
- K44K (p.Lys44Lys), rs2102307834, gnomAD 1-161328450-G-A, CADD 11.30
- N45D (p.Asn45Asp), rs2526364926, ClinGen CA343361141, ClinVar RCV002791365, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- N45R (p.Asn45Arg), gnomAD 1-161328451-A-AG, CADD 26.50
- N45S (p.Asn45Ser), gnomAD 1-161328452-A-G, REVEL 0.66, MetaLR 0.93
- I46T (p.Ile46Thr), rs2526365022, ClinGen CA343361170, ClinVar RCV003033011, ClinVar RCV004673775, Conflicting interpretations, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor; Hered
- I46V (p.Ile46Val), rs1558167321, ClinGen CA343361165, ClinVar RCV000704346, ClinVar RCV002386263, REVEL 0.14, MetaLR 0.44, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Gastrointestinal stromal
- I46R (p.Ile46Arg), gnomAD 1-161328455-T-G, REVEL 0.26, MetaLR 0.48
- G47A (p.Gly47Ala), rs1571851599, ClinGen CA343361187, ClinVar RCV000794414, ClinVar RCV004659205, AlphaMissense 0.10, MetaLR 0.53, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor; Pheochr
- G47C (p.Gly47Cys), Ensembl rs1222718805
- G47D (p.Gly47Asp), rs1571851599, ClinGen CA343361185, ClinVar RCV003377760, NCI-TCGA Cosmic COSV1007, AlphaMissense 0.10, MetaLR 0.53, Uncertain significance, Hereditary cancer-predisposing syndrome
- G47R (p.Gly47Arg), Ensembl rs1222718805
- G47S (p.Gly47Ser), rs1222718805, ClinGen CA343361178, ClinVar RCV003006350, AlphaMissense 0.10, MetaLR 0.28, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- G47V (p.Gly47Val), Ensembl rs1571851599, MetaLR 0.53, MetaSVM -0.50, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; not provided; Pheochromocytoma/pa
- S48L (p.Ser48Leu), rs1362354860, ClinGen CA343361202, NCI-TCGA Cosmic COSV6136, cosmic curated COSV61369, AlphaMissense 0.07, MetaLR 0.50, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 3; Gastrointestinal stromal tumor
- S48P (p.Ser48Pro), Ensembl rs2102307875, MetaLR 0.93, MetaSVM 0.98
- N49D (p.Asn49Asp), rs2526365156, ClinGen CA343361210, ClinVar RCV002394770, ClinVar RCV004007321, Uncertain significance, Gastrointestinal stromal tumor; Hereditary cancer-predisposing syndrome; Heredit
- N49I (p.Asn49Ile), rs1571851610, ClinGen CA343361216, ClinVar RCV002016061, ClinVar RCV003161185, AlphaMissense 0.08, MetaLR 0.83, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Gastrointestinal stromal
- N49S (p.Asn49Ser), rs1571851610, ClinGen CA343361215, ClinVar RCV000807849, ClinVar RCV004569647, AlphaMissense 0.08, MetaLR 0.83, Uncertain significance, Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3
- N49T (p.Asn49Thr), rs1571851610, ClinGen CA343361214, ClinVar RCV001011750, ClinVar RCV003473568, AlphaMissense 0.08, MetaLR 0.83, Uncertain significance, Hereditary cancer-predisposing syndrome; Gastrointestinal stromal tumor
Public SDHC analysis runs
- SDHC analysis run — SDHC (515 variants) — completed 2026-08-22