SDHAF2 (Q9NX18) variants and mutations
SDHAF2 (also known as Q9NX18) is a human protein-coding gene encoding a succinate dehydrogenase assembly factor 2, mitochondrial protein. It is required for covalent flavin attachment and maturation of the SDHA catalytic subunit, enabling normal succinate dehydrogenase activity. Germline loss-of-function variants can predispose to hereditary head-and-neck paragangliomas through functional loss of complex II. This analysis covers 515 SDHAF2 variants and mutations. Of these, 80% have computational variant effect predictions. Disease context includes hereditary pheochromocytoma-paraganglioma, pheochromocytoma/paraganglioma syndrome 2, and hereditary neoplastic syndrome. Example SDHAF2 variants include M1I, M1T, and A2E.
Variant analysis overview
- Gene: SDHAF2
- Protein: Q9NX18
- UniProt accession: Q9NX18
- Organism: Homo sapiens
- Variants analyzed: 515
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 380 unspecified-consequence records; 61 synonymous variants; 14 frameshift variants; 51 missense variants; 3 stop-gained variants; 3 splice-region variants; 3 in-frame deletions; 5 stop lost; 2 substitution
- Prediction scores: 414 variants have prediction scores (80% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hereditary pheochromocytoma-paraganglioma, pheochromocytoma/paraganglioma syndrome 2, hereditary neoplastic syndrome, Inherited cancer-predisposing syndrome, paraganglioma, ovarian endometrioid adenocarcinoma with squamous differentiation, neuroendocrine carcinoma, malignant endocrine neoplasm, bile duct carcinoma, carcinoma of liver and intrahepatic biliary tract, non-small cell lung carcinoma, breast carcinoma.
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 SDHAF2 variants
Examples include M1I, M1T, A2E, A2S, A2T, A2V, A2A, V3A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1861835884, ClinGen CA380680087, ClinVar RCV001223536, ClinVar RCV002375214, MetaLR 0.54, MetaSVM -0.32, Uncertain significance, not provided
- M1T (p.Met1Thr), rs1060503392, ClinGen CA16613424, ClinVar RCV000469697, ClinVar RCV001017953, MetaLR 0.52, MetaSVM -0.39, Conflicting interpretations, Pheochromocytoma/paraganglioma syndrome 2; Hereditary cancer-predisposing syndro
- A2E (p.Ala2Glu), rs867394650, ClinGen CA380680100, ClinVar RCV003472632, ClinVar RCV004661665, REVEL 0.41, MetaLR 0.39, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- A2S (p.Ala2Ser), rs2540110793, ClinGen CA380680099, ClinVar RCV003168302, Uncertain significance, Hereditary cancer-predisposing syndrome
- A2T (p.Ala2Thr), rs2540110793, ClinGen CA380680095, ClinVar RCV003634761, REVEL 0.37, MetaLR 0.29, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A2V (p.Ala2Val), rs867394650, ClinGen CA222873795, ClinVar RCV002943115, ClinVar RCV003382973, REVEL 0.39, MetaLR 0.35, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Hereditary pheochromocyto
- A2A (p.Ala2Ala), rs747571875, gnomAD 11-61430152-G-T, CADD 7.43
- V3A (p.Val3Ala), rs760006057, ClinGen CA059606, ClinVar RCV001219732, ClinVar RCV002375198, REVEL 0.12, MetaLR 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- V3E (p.Val3Glu), ExAC rs760006057, gnomAD rs760006057, Uncertain significance
- V3G (p.Val3Gly), ExAC rs760006057, gnomAD rs760006057, Uncertain significance
- V3L (p.Val3Leu), rs149277592, ClinGen CA059579, ClinVar RCV000476593, ClinVar RCV000483780, REVEL 0.15, MetaLR 0.29, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- V3M (p.Val3Met), rs149277592, ClinGen CA380680112, cosmic curated COSV57099, ClinVar RCV000572705, REVEL 0.07, MetaLR 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome
- S4A (p.Ser4Ala), rs1205348193, ClinGen CA380680124, ClinVar RCV001348986, TOPMed rs1205348193, AlphaMissense 0.05, MetaLR 0.15, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S4C (p.Ser4Cys), rs778449586, ClinGen CA057758, ClinVar RCV000801877, ClinVar RCV001010273, REVEL 0.18, MetaLR 0.19, Conflicting interpretations, Hereditary pheochromocytoma and paraganglioma; Pheochromocytoma/paraganglioma sy
- S4F (p.Ser4Phe), rs778449586, ClinGen CA222873825, ClinVar RCV002011703, ClinVar RCV004770370, REVEL 0.22, MetaLR 0.23, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; not provided; Hereditary cancer-p
- S4P (p.Ser4Pro), NCI-TCGA Cosmic COSV5709, cosmic curated COSV57099, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S4L (p.Ser4Leu), gnomAD 11-61430152-GGTGT, CADD 23.10
- S4S (p.Ser4Ser), rs2135436188, gnomAD 11-61430158-T-A, CADD 4.50
- T5A (p.Thr5Ala), rs775763888, ClinGen CA057802, cosmic curated COSV57098, ClinVar RCV000457612, REVEL 0.16, MetaLR 0.17, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- T5I (p.Thr5Ile), rs1861837207, ClinGen CA380680138, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10007, AlphaMissense 0.14, MetaLR 0.36, Uncertain significance, not provided; Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-p
- T5S (p.Thr5Ser), gnomAD 11-61430159-A-T, REVEL 0.20, MetaLR 0.14
- T5R (p.Thr5Arg), gnomAD 11-61430160-C-G, REVEL 0.25, MetaLR 0.35
- T5T (p.Thr5Thr), rs144511254, gnomAD 11-61430161-A-G, CADD 1.04
- V6A (p.Val6Ala), rs1565125251, ClinGen CA380680157, ClinVar RCV001236138, ClinVar RCV005269005, AlphaMissense 0.18, MetaLR 0.36, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- V6E (p.Val6Glu), Ensembl rs1565125251, REVEL 0.21, AlphaMissense 0.18, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- V6G (p.Val6Gly), rs1565125251, ClinGen CA380680159, ClinVar RCV003838940, ClinVar RCV004366875, AlphaMissense 0.18, MetaLR 0.36, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- V6L (p.Val6Leu), NCI-TCGA Cosmic COSV5709, cosmic curated COSV57099, Variant assessed as somatic; moderate impact.
- V6M (p.Val6Met), TOPMed rs1337661888, gnomAD rs1337661888, REVEL 0.16, MetaLR 0.36, Uncertain significance, Hereditary cancer-predisposing syndrome
- F7L (p.Phe7Leu), rs892955355, ClinGen CA380680173, ClinVar RCV003071563, REVEL 0.11, MetaLR 0.17, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- F7S (p.Phe7Ser), rs1311192006, ClinGen CA380680170, ClinVar RCV003380337, AlphaMissense 0.16, MetaLR 0.26, Uncertain significance, Hereditary cancer-predisposing syndrome
- F7V (p.Phe7Val), rs2540110932, ClinGen CA380680166, ClinVar RCV002807021, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- F7Y (p.Phe7Tyr), rs1311192006, ClinGen CA380680168, ClinVar RCV003634657, Ensembl rs1311192006, AlphaMissense 0.16, MetaLR 0.26, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- F7F (p.Phe7Phe), rs892955355, gnomAD 11-61430167-C-T, CADD 6.19
- S8* (p.Ser8Ter), rs1254052531, ClinGen CA380680185, ClinVar RCV001015411, ClinVar RCV002549418, CADD 35.00, Pathogenic
- S8L (p.Ser8Leu), rs1254052531, ClinGen CA380680187, ClinVar RCV001874902, ClinVar RCV002449511, REVEL 0.08, MetaLR 0.26, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- S8P (p.Ser8Pro), rs2540110958, ClinGen CA380680182, ClinVar RCV002446315, REVEL 0.17, MetaLR 0.15, Likely benign, Hereditary cancer-predisposing syndrome
- S8T (p.Ser8Thr), rs2540110958, ClinGen CA380680179, ClinVar RCV002428471, Uncertain significance, Hereditary cancer-predisposing syndrome
- S8W (p.Ser8Trp), rs1254052531, ClinGen CA380680189, ClinVar RCV002430667, ClinVar RCV004765517, REVEL 0.19, MetaLR 0.22, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Hereditary pheochromocyto
- S8S (p.Ser8Ser), rs764251580, gnomAD 11-61430170-G-A, CADD 4.44
- T9A (p.Thr9Ala), rs1554983610, ClinGen CA380680194, cosmic curated COSV57100, ClinVar RCV000547322, AlphaMissense 0.06, MetaLR 0.14, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- T9I (p.Thr9Ile), rs552102107, ClinGen CA058331, ClinVar RCV001983169, ClinVar RCV002441107, REVEL 0.09, AlphaMissense 0.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- T9S (p.Thr9Ser), rs552102107, ClinGen CA380680198, ClinVar RCV003634813, AlphaMissense 0.10, MetaLR 0.28, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S10L (p.Ser10Leu), rs1590759653, ClinGen CA380680204, NCI-TCGA Cosmic COSV5709, cosmic curated COSV57098, REVEL 0.24, AlphaMissense 0.09, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 2; Hereditary cancer-predisposing syndro
- S10T (p.Ser10Thr), rs1861838801, ClinGen CA380680200, ClinVar RCV001351066, gnomAD rs1861838801, REVEL 0.16, MetaLR 0.20, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S10W (p.Ser10Trp), rs1590759653, ClinGen CA380680205, ClinVar RCV003181765, AlphaMissense 0.09, MetaLR 0.16, Uncertain significance, Hereditary cancer-predisposing syndrome
- S10R (p.Ser10Arg), rs1861838658, gnomAD 11-61430172-CT-C, CADD 19.40
- S10C (p.Ser10Cys), rs1339037960, gnomAD 11-61430174-TC-T, CADD 24.80
- S10* (p.Ser10Ter), gnomAD 11-61430175-C-A, CADD 37.00
- S11* (p.Ser11Ter), rs148425779, ClinGen CA222873842, ClinVar RCV003069774, ClinVar RCV004071868, CADD 37.00, Pathogenic
- S11L (p.Ser11Leu), rs148425779, ClinGen CA058473, cosmic curated COSV57099, ClinVar RCV000540123, REVEL 0.15, MetaLR 0.26, Benign/Likely benign, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- S11W (p.Ser11Trp), rs148425779, ClinGen CA380680213, ClinVar RCV001896081, ClinVar RCV002458741, REVEL 0.24, MetaLR 0.24, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Pheochromocytoma/paraganglioma sy
- S11P (p.Ser11Pro), gnomAD 11-61430177-T-C, REVEL 0.15, MetaLR 0.22
- S11S (p.Ser11Ser), rs1467342573, gnomAD 11-61430179-G-A, CADD 8.05
- L12* (p.Leu12Ter), rs2540111054, ClinGen CA2580084350, ClinVar RCV002452035, Uncertain significance
- L12P (p.Leu12Pro), rs1590759677, ClinGen CA380680221, ClinVar RCV000824143, ClinVar RCV002453904, REVEL 0.18, AlphaMissense 0.09, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- L12Q (p.Leu12Gln), rs1590759677, ClinGen CA380680219, ClinVar RCV002301736, AlphaMissense 0.09, MetaLR 0.31, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- L12V (p.Leu12Val), rs2135436365, ClinGen CA380680217, ClinVar RCV003516999, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- L12M (p.Leu12Met), gnomAD 11-61430180-C-A, REVEL 0.16, MetaLR 0.32
- L12L (p.Leu12Leu), gnomAD 11-61430182-G-T, CADD 24.90
- M13I (p.Met13Ile), rs2540123981, ClinGen CA380682728, ClinVar RCV003472633, ClinVar RCV004364797, REVEL 0.13, MetaLR 0.24, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma/paraganglioma syndrome
- M13L (p.Met13Leu), rs1361460244, ClinGen CA380682716, ClinVar RCV000573855, ClinVar RCV000689080, REVEL 0.16, MetaLR 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- M13T (p.Met13Thr), TOPMed rs1862008982
- M13V (p.Met13Val), rs1361460244, ClinGen CA380682714, ClinVar RCV001227902, ClinVar RCV004032619, REVEL 0.14, MetaLR 0.13, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- L14F (p.Leu14Phe), rs1273048863, ClinGen CA380682741, ClinVar RCV001964778, ClinVar RCV003382735, REVEL 0.32, MetaLR 0.50, Uncertain significance, not provided; Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-p
- A15D (p.Ala15Asp), NCI-TCGA Cosmic COSV5709, cosmic curated COSV57099, Variant assessed as somatic; moderate impact.
- A15P (p.Ala15Pro), rs1002894711, ClinGen CA380682755, ClinVar RCV001064541, ClinVar RCV004030541, AlphaMissense 0.10, MetaLR 0.32, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- A15S (p.Ala15Ser), rs1002894711, ClinGen CA222877253, ClinVar RCV000639333, Ensembl rs1002894711, AlphaMissense 0.10, MetaLR 0.32, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A15G (p.Ala15Gly), gnomAD 11-61437632-C-G, REVEL 0.12, MetaLR 0.28
- A15A (p.Ala15Ala), rs770012985, gnomAD 11-61437633-T-C, CADD 3.07
- L16V (p.Leu16Val), rs1312422519, ClinGen CA380682770, ClinVar RCV001228955, gnomAD rs1312422519, REVEL 0.09, MetaLR 0.21, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- L16L (p.Leu16Leu), rs1312422519, gnomAD 11-61437634-C-T, CADD 2.13
- S17* (p.Ser17Ter), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10007, Variant assessed as somatic; high impact.
- S17L (p.Ser17Leu), rs1216278309, ClinGen CA380682790, ClinVar RCV003516812, TOPMed rs1216278309, AlphaMissense 0.16, MetaLR 0.35, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- S17P (p.Ser17Pro), rs2540123995, ClinGen CA380682778, ClinVar RCV002343024, ClinVar RCV003776012, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- R18G (p.Arg18Gly), rs200911550, ClinGen CA017332, ClinVar RCV000034763, ClinVar RCV000568645, REVEL 0.10, MetaLR 0.36, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- R18K (p.Arg18Lys), rs1862009340, ClinGen CA380682801, ClinVar RCV001342533, Ensembl rs1862009340, AlphaMissense 0.11, MetaLR 0.29, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- R18S (p.Arg18Ser), NCI-TCGA TCGA novel, gnomAD rs1590764725, Variant assessed as somatic; moderate impact.
- R18R (p.Arg18Arg), rs1590764725, gnomAD 11-61437642-G-A, CADD 5.82
- H19Y (p.His19Tyr), gnomAD 11-61437643-C-T, REVEL 0.19, MetaLR 0.30
- S20N (p.Ser20Asn), rs2134892121, ClinGen CA380682839, ClinVar RCV003633837, REVEL 0.20, MetaLR 0.25, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S20R (p.Ser20Arg), rs2540124020, ClinGen CA380682830, ClinVar RCV004522225, REVEL 0.20, MetaLR 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome
- S20T (p.Ser20Thr), Ensembl rs2134892121
- S20G (p.Ser20Gly), gnomAD 11-61437646-A-G, REVEL 0.08, MetaLR 0.27
- L21R (p.Leu21Arg), rs2540124034, ClinGen CA380682852, ClinVar RCV003517097, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- L21V (p.Leu21Val), gnomAD 11-61437649-C-G, REVEL 0.10, MetaLR 0.35
- L21L (p.Leu21Leu), rs191513932, gnomAD 11-61437651-A-G, CADD 0.26
- L22F (p.Leu22Phe), rs766468929, ExAC rs766468929, gnomAD rs766468929, ClinGen CA059536, REVEL 0.08, MetaLR 0.26, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- L22L (p.Leu22Leu), rs766468929, gnomAD 11-61437654-G-A, CADD 1.58
- P24H (p.Pro24His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P24L (p.Pro24Leu), rs2540124048, ClinGen CA380682896, ClinVar RCV003472631, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 2
- P24S (p.Pro24Ser), rs2540124046, ClinGen CA380682890, ClinVar RCV004522226, NCI-TCGA Cosmic COSV5709, REVEL 0.26, MetaLR 0.44, Uncertain significance, Hereditary cancer-predisposing syndrome
- P24P (p.Pro24Pro), gnomAD 11-61437660-T-C, CADD 7.95
- L25F (p.Leu25Phe), rs2134892142, ClinGen CA380682912, ClinVar RCV003301602, Uncertain significance, Hereditary cancer-predisposing syndrome
- L25S (p.Leu25Ser), rs2540124051, ClinGen CA380682907, ClinVar RCV003301601, Uncertain significance, Hereditary cancer-predisposing syndrome
- L25L (p.Leu25Leu), rs2134892142, gnomAD 11-61437663-G-A, CADD 3.77
- L26F (p.Leu26Phe), rs751530375, ClinGen CA380682920, ClinVar RCV004522227, AlphaMissense 0.07, MetaLR 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome
- L26V (p.Leu26Val), ExAC rs751530375, gnomAD rs751530375, Uncertain significance, Hereditary cancer-predisposing syndrome
- L26L (p.Leu26Leu), rs2134892152, gnomAD 11-61437666-C-G, CADD 5.10
- S27G (p.Ser27Gly), rs2134892157, ClinGen CA380682933, ClinVar RCV001864919, ClinVar RCV005482930, AlphaMissense 0.06, MetaLR 0.23, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- S27I (p.Ser27Ile), ExAC rs759472787, TOPMed rs759472787, gnomAD rs759472787, REVEL 0.09, MetaLR 0.32, Likely benign
- S27N (p.Ser27Asn), rs759472787, ClinGen CA059592, ClinVar RCV000639347, ClinVar RCV001027179, REVEL 0.12, MetaLR 0.26, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- V28E (p.Val28Glu), rs1590764751, ClinGen CA380682952, ClinVar RCV001017709, ClinVar RCV001873301, AlphaMissense 0.06, MetaLR 0.18, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- V28G (p.Val28Gly), rs1590764751, ClinGen CA380682957, ClinVar RCV001225041, ClinVar RCV003373056, REVEL 0.14, AlphaMissense 0.06, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- V28M (p.Val28Met), rs1303104521, ClinGen CA380682945, ClinVar RCV001898054, ClinVar RCV004656710, REVEL 0.19, MetaLR 0.22, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- T29S (p.Thr29Ser), gnomAD 11-61437673-A-T, REVEL 0.08, MetaLR 0.18
- T29T (p.Thr29Thr), gnomAD 11-61437675-A-G, CADD 7.56
- S30* (p.Ser30Ter), rs2540124080, ClinGen CA380682984, ClinVar RCV002846684, Pathogenic
- S30L (p.Ser30Leu), NCI-TCGA Cosmic COSV5710, cosmic curated COSV57100, Variant assessed as somatic; moderate impact.
- S30P (p.Ser30Pro), rs1312756692, ClinGen CA380682979, ClinVar RCV003037700, ClinVar RCV006449067, AlphaMissense 0.08, MetaLR 0.24, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; not provided
- S30T (p.Ser30Thr), gnomAD rs1312756692, REVEL 0.13, AlphaMissense 0.08
- F31L (p.Phe31Leu), ExAC rs752477657, gnomAD rs752477657, REVEL 0.10, MetaLR 0.27, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided
- F31V (p.Phe31Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R32G (p.Arg32Gly), Ensembl rs2134892180
- R32I (p.Arg32Ile), gnomAD rs1277577700, Uncertain significance
- R32K (p.Arg32Lys), rs1277577700, ClinGen CA380683020, ClinVar RCV003181767, ClinVar RCV005101018, AlphaMissense 0.13, MetaLR 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- R32S (p.Arg32Ser), rs952830677, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10007, ClinGen CA222877279, REVEL 0.06, MetaLR 0.24, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Pheochromocytoma/paragang
- R32T (p.Arg32Thr), gnomAD rs1277577700, REVEL 0.26, AlphaMissense 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome
- R33C (p.Arg33Cys), rs144867876, ClinGen CA017340, cosmic curated COSV57100, ClinVar RCV000034764, REVEL 0.24, MetaLR 0.40, Benign/Likely benign, Hereditary cancer-predisposing syndrome; not specified; not provided
- R33H (p.Arg33His), rs777442412, ClinGen CA059634, ClinVar RCV000639349, ClinVar RCV001579475, REVEL 0.32, AlphaMissense 0.17, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; not provided
- R33L (p.Arg33Leu), rs777442412, ClinGen CA380683038, ClinVar RCV000800389, ClinVar RCV001019878, AlphaMissense 0.17, MetaLR 0.43, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- R33R (p.Arg33Arg), rs753325226, gnomAD 11-61437687-C-T, CADD 9.23
- F34L (p.Phe34Leu), rs756917732, ClinGen CA057734, ClinVar RCV001037693, ClinVar RCV002434440, REVEL 0.12, AlphaMissense 0.11, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- F34S (p.Phe34Ser), rs1862010056, ClinGen CA380683051, ClinVar RCV001059233, Ensembl rs1862010056, AlphaMissense 0.11, MetaLR 0.17, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- F34V (p.Phe34Val), rs756917732, ClinGen CA380683046, ClinVar RCV001016986, ClinVar RCV001320391, AlphaMissense 0.11, MetaLR 0.32, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- Y35* (p.Tyr35Ter), Ensembl rs2134892231
- Y35C (p.Tyr35Cys), TOPMed rs1330914865, Uncertain significance
- Y35H (p.Tyr35His), rs1590764776, ClinGen CA380683065, ClinVar RCV001042027, ClinVar RCV002391124, REVEL 0.48, MetaLR 0.63, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- Y35S (p.Tyr35Ser), rs1330914865, ClinGen CA380683070, ClinVar RCV002012550, ClinVar RCV002389004, AlphaMissense 0.19, MetaLR 0.63, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- Y35Y (p.Tyr35Tyr), gnomAD 11-61437693-C-T, CADD 9.67
- R36G (p.Arg36Gly), rs1413272315, ClinGen CA380683082, ClinVar RCV000700909, ClinVar RCV001017188, REVEL 0.42, MetaLR 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- R36T (p.Arg36Thr), gnomAD 11-61437695-G-C, REVEL 0.38, MetaLR 0.34
- G37C (p.Gly37Cys), rs868016844, ClinGen CA380683103, ClinVar RCV000533916, ClinVar RCV005268647, AlphaMissense 0.40, MetaLR 0.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- G37S (p.Gly37Ser), rs868016844, ClinGen CA222877291, ClinVar RCV003837688, Ensembl rs868016844, AlphaMissense 0.40, MetaLR 0.70, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- G37G (p.Gly37Gly), gnomAD 11-61437699-T-G, CADD 9.62
- D38E (p.Asp38Glu), Ensembl rs2134892239, Conflicting interpretations, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- D38H (p.Asp38His), rs2540124128, ClinGen CA380683112, ClinVar RCV004012541, REVEL 0.31, MetaLR 0.41, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- D38N (p.Asp38Asn), rs2540124128, ClinGen CA380683117, ClinVar RCV003517683, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- D38G (p.Asp38Gly), gnomAD 11-61437701-A-G, REVEL 0.28, MetaLR 0.34
- S39G (p.Ser39Gly), rs2540124136, ClinGen CA380683139, ClinVar RCV002321114, ClinVar RCV003775763, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- S39N (p.Ser39Asn), rs2134892250, ClinGen CA380683142, ClinVar RCV001995955, Ensembl rs2134892250, AlphaMissense 0.36, MetaLR 0.43, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S39R (p.Ser39Arg), ExAC rs780593356, gnomAD rs780593356, REVEL 0.33, MetaLR 0.44, Uncertain significance, Hereditary cancer-predisposing syndrome
- P40L (p.Pro40Leu), rs2540124144, ClinGen CA380683166, ClinVar RCV002617850, ClinVar RCV006292217, REVEL 0.25, MetaLR 0.41, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- P40S (p.Pro40Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T41A (p.Thr41Ala), rs1455092335, ClinGen CA380683173, ClinVar RCV001208813, ClinVar RCV003294012, REVEL 0.15, MetaLR 0.20, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- T41I (p.Thr41Ile), rs747508289, ClinGen CA057768, ClinVar RCV002369185, ClinVar RCV003776305, REVEL 0.25, AlphaMissense 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- T41K (p.Thr41Lys), rs747508289, ClinGen CA380683176, ClinVar RCV003181766, AlphaMissense 0.13, MetaLR 0.38, Uncertain significance, Hereditary cancer-predisposing syndrome
- T41R (p.Thr41Arg), rs747508289, ClinGen CA380683180, ClinVar RCV001973967, ExAC rs747508289, AlphaMissense 0.13, MetaLR 0.38, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- D42N (p.Asp42Asn), rs2134892260, ClinGen CA380683183, ClinVar RCV001977638, ClinVar RCV006280866, AlphaMissense 0.22, MetaLR 0.47, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- D42D (p.Asp42Asp), rs1590764790, gnomAD 11-61437714-T-C, CADD 9.76
- S43F (p.Ser43Phe), rs2540124157, ClinGen CA380683212, ClinVar RCV003387082, ClinVar RCV003517490, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- S43S (p.Ser43Ser), gnomAD 11-61437717-C-T, CADD 9.67
- Q44* (p.Gln44Ter), rs2134892271, ClinGen CA380683220, ClinVar RCV001581492, ClinVar RCV001866107, CADD 36.00, Pathogenic
- Q44P (p.Gln44Pro), rs2540124170, ClinGen CA380683228, ClinVar RCV003634544, REVEL 0.32, MetaLR 0.37, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- Q44K (p.Gln44Lys), Ensembl rs2134892271, Pathogenic
- Q44R (p.Gln44Arg), rs2540124170, ClinGen CA380683224, ClinVar RCV002385641, ClinVar RCV003149030, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- Q44Q (p.Gln44Gln), rs2134892277, gnomAD 11-61437720-A-G, CADD 6.91
- K45E (p.Lys45Glu), rs368945911, ClinGen CA057782, ClinVar RCV000639338, ClinVar RCV002386043, REVEL 0.27, MetaLR 0.32, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- K45K (p.Lys45Lys), rs1590764800, gnomAD 11-61437723-G-A, CADD 7.14
- D46E (p.Asp46Glu), rs969049910, ClinGen CA380683273, ClinVar RCV000639354, ClinVar RCV003303021, REVEL 0.36, MetaLR 0.44, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- D46N (p.Asp46Asn), rs1590764803, ClinGen CA380683257, ClinVar RCV000809871, ClinVar RCV003372864, AlphaMissense 0.39, MetaLR 0.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- D46D (p.Asp46Asp), rs969049910, gnomAD 11-61437726-C-T, CADD 6.65
- M47I (p.Met47Ile), ExAC rs748505431, gnomAD rs748505431
- M47L (p.Met47Leu), rs111402137, ClinGen CA380683279, ClinVar RCV003301600, AlphaMissense 0.06, MetaLR 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome
- M47V (p.Met47Val), rs111402137, ClinGen CA057795, ClinVar RCV000566506, ClinVar RCV000703323, REVEL 0.22, AlphaMissense 0.06, Uncertain significance, Pheochromocytoma/paraganglioma syndrome 2; Hereditary cancer-predisposing syndro
- I48T (p.Ile48Thr), rs1590764818, ClinGen CA380683305, ClinVar RCV001011590, Ensembl rs1590764818, AlphaMissense 0.17, MetaLR 0.32, Uncertain significance, Hereditary cancer-predisposing syndrome
- I48V (p.Ile48Val), gnomAD 11-61437730-A-G, REVEL 0.19, MetaLR 0.29
- E49A (p.Glu49Ala), TOPMed rs1295134579, gnomAD rs1295134579, REVEL 0.40, MetaLR 0.35, Uncertain significance
- E49G (p.Glu49Gly), rs1295134579, ClinGen CA380683324, ClinVar RCV001053733, ClinVar RCV001772266, REVEL 0.51, MetaLR 0.56, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- E49del (p.Glu49del), rs749431351, gnomAD 11-61437732-TGAA-, CADD 21.80
- P51H (p.Pro51His), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10007, gnomAD rs1371376884, Uncertain significance
- P51L (p.Pro51Leu), rs1371376884, ClinGen CA380683358, ClinVar RCV001901632, ClinVar RCV002397880, REVEL 0.43, MetaLR 0.50, Uncertain significance, not provided; Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-p
- P51R (p.Pro51Arg), rs1371376884, ClinGen CA380683356, ClinVar RCV004012389, ClinVar RCV005734660, REVEL 0.50, MetaLR 0.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- P51S (p.Pro51Ser), rs1862010801, ClinGen CA380683351, ClinVar RCV001318585, ClinVar RCV004671336, AlphaMissense 0.25, MetaLR 0.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- P51P (p.Pro51Pro), gnomAD 11-61437741-T-C, CADD 9.05
- L52F (p.Leu52Phe), gnomAD 11-61437744-G-T, REVEL 0.51, MetaLR 0.62
- L52L (p.Leu52Leu), rs773466310, gnomAD 11-61437744-G-A, CADD 9.94
- P53L (p.Pro53Leu), rs562958122, ClinGen CA017313, ClinVar RCV001216373, ClinVar RCV002399667, REVEL 0.58, AlphaMissense 0.51, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- P53R (p.Pro53Arg), rs562958122, ClinGen CA380683390, ClinVar RCV002301708, AlphaMissense 0.51, MetaLR 0.61, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- P53S (p.Pro53Ser), rs1060503390, ClinGen CA16613649, ClinVar RCV000460874, ClinVar RCV001012279, REVEL 0.44, AlphaMissense 0.85, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- P53T (p.Pro53Thr), rs1060503390, ClinGen CA380683382, ClinVar RCV001300202, ClinVar RCV005271126, AlphaMissense 0.85, MetaLR 0.57, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
Public SDHAF2 analysis runs
- SDHAF2 analysis run — SDHAF2 (515 variants) — completed 2026-08-22