VHL (P40337) variants and mutations
VHL (also known as P40337) is a human protein-coding gene encoding a von Hippel-Lindau disease tumor suppressor protein. It targets hydroxylated HIF-alpha proteins for ubiquitin-mediated degradation when oxygen is sufficient, keeping hypoxia-response programs suppressed. Loss of function stabilizes HIF signaling and causes von Hippel-Lindau tumor-predisposition syndrome while also driving most clear-cell renal carcinomas. This analysis covers 1,319 VHL variants and mutations. Of these, 67% have computational variant effect predictions. Disease context includes von Hippel-Lindau disease, Chuvash polycythemia, and pheochromocytoma. Example VHL variants include M1?, M1I, and M1K.
Variant analysis overview
- Gene: VHL
- Protein: P40337
- UniProt accession: P40337
- Organism: Homo sapiens
- Variants analyzed: 1319
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 1,150 unspecified-consequence records; 111 synonymous variants; 4 frameshift variants; 42 missense variants; 7 in-frame deletions; 1 stop-gained variants; 1 in-frame insertions; 2 splice-region variants; 1 substitution
- Prediction scores: 890 variants have prediction scores (67% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: von Hippel-Lindau disease, Chuvash polycythemia, pheochromocytoma, hereditary pheochromocytoma-paraganglioma, Chuvash erythrocytosis, clear cell renal carcinoma, nonpapillary renal cell carcinoma, hereditary neoplastic syndrome, Inherited cancer-predisposing syndrome, renal cell carcinoma, neurodegenerative disease, renal 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 VHL variants
Examples include M1?, M1I, M1K, M1L, M1V, P2A, P2H, P2L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, rs578091032, ClinGen CA040825, NCI-TCGA Cosmic COSV5654, NCI-TCGA Cosmic COSV9907, MetaLR 0.37, MetaSVM -0.63, Likely benign
- M1I (p.Met1Ile), rs578091032, ClinGen CA70042122, ClinVar RCV000707210, ClinVar RCV002369974, MetaLR 0.37, MetaSVM -0.63, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- M1K (p.Met1Lys), rs2125124372, ClinGen CA351747011, ClinVar RCV003049076, MetaLR 0.39, MetaSVM -0.33, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- M1L (p.Met1Leu), rs1060503557, ClinGen CA16611052, ClinVar RCV000458939, ClinVar RCV000579235, MetaLR 0.27, MetaSVM -0.71, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia
- M1V (p.Met1Val), rs1060503557, ClinGen CA351747010, ClinVar RCV000662755, ClinVar RCV001230391, MetaLR 0.27, MetaSVM -0.71, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- P2A (p.Pro2Ala), rs1034974221, ClinGen CA351747015, ClinVar RCV001023393, ClinVar RCV002551875, REVEL 0.12, MetaLR 0.35, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- P2H (p.Pro2His), rs111246617, ClinGen CA351747016, ClinVar RCV002880327, ClinVar RCV003167844, AlphaMissense 0.24, MetaLR 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- P2L (p.Pro2Leu), rs111246617, ClinGen CA020518, ClinVar RCV000161089, ClinVar RCV000168429, REVEL 0.27, AlphaMissense 0.24, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Nonpapillary renal cell carcin
- P2R (p.Pro2Arg), rs111246617, ClinGen CA16611054, ClinVar RCV000460146, ClinVar RCV002256271, REVEL 0.29, AlphaMissense 0.24, Uncertain significance, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- P2S (p.Pro2Ser), rs1034974221, ClinGen CA70042126, ClinVar RCV000696229, ClinVar RCV000997984, REVEL 0.21, MetaLR 0.34, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- P2T (p.Pro2Thr), rs1034974221, ClinGen CA351747014, ClinVar RCV003792456, REVEL 0.21, MetaLR 0.35, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- P2P (p.Pro2Pro), rs1014417508, gnomAD 3-10141853-C-G, CADD 8.82
- R3G (p.Arg3Gly), rs878854130, ClinGen CA351747017, ClinVar RCV001338748, ClinVar RCV002418995, AlphaMissense 0.15, MetaLR 0.31, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- R3L (p.Arg3Leu), TOPMed rs1178481595, gnomAD rs1178481595, Uncertain significance
- R3P (p.Arg3Pro), rs1178481595, ClinGen CA351747019, ClinVar RCV000698072, ClinVar RCV002257940, REVEL 0.31, MetaLR 0.32, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; not provided
- R3Q (p.Arg3Gln), rs1178481595, ClinGen CA351747018, ClinVar RCV001901781, ClinVar RCV002370494, REVEL 0.14, MetaLR 0.33, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- R3W (p.Arg3Trp), rs878854130, ClinGen CA10582110, ClinVar RCV000226904, ClinVar RCV002418000, REVEL 0.16, AlphaMissense 0.15, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- R3R (p.Arg3Arg), gnomAD 3-10141854-C-A, CADD 6.12
- R4G (p.Arg4Gly), rs886057702, ClinGen CA351747021, ClinVar RCV001976403, ClinVar RCV005772306, REVEL 0.15, MetaLR 0.34, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- R4K (p.Arg4Lys), rs886057703, ClinGen CA351747022, ClinVar RCV004520895, ClinVar RCV006551186, REVEL 0.19, MetaLR 0.24, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome
- R4L (p.Arg4Leu), rs1575920840, ClinGen CA915941833, ClinVar RCV001009648, ClinVar RCV001860608, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- R4M (p.Arg4Met), rs886057703, ClinGen CA10616745, ClinVar RCV000375604, ClinVar RCV001350502, REVEL 0.29, MetaLR 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- R4W (p.Arg4Trp), rs886057702, ClinGen CA10614386, ClinVar RCV000316395, gnomAD rs886057702, REVEL 0.25, MetaLR 0.42, Uncertain significance, Von Hippel-Lindau syndrome
- R4A (p.Arg4Ala), rs1559425474, gnomAD 3-10141853-C-CCGG, CADD 18.80
- R4R (p.Arg4Arg), rs1553619274, gnomAD 3-10141859-G-A, CADD 13.10
- A5G (p.Ala5Gly), ExAC rs755333116, TOPMed rs755333116, gnomAD rs755333116, Uncertain significance, Hereditary cancer-predisposing syndrome
- A5P (p.Ala5Pro), rs1559425498, ClinGen CA351747027, ClinVar RCV000685222, Ensembl rs1559425498, AlphaMissense 0.09, MetaLR 0.35, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- A5S (p.Ala5Ser), rs1559425498, ClinGen CA351747028, ClinVar RCV002046234, ClinVar RCV002391137, REVEL 0.11, AlphaMissense 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- A5T (p.Ala5Thr), rs1559425498, ClinGen CA351747026, ClinVar RCV003466536, ClinVar RCV005515563, AlphaMissense 0.09, MetaLR 0.35, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia
- A5V (p.Ala5Val), rs755333116, ClinGen CA039495, cosmic curated COSV56544, ClinVar RCV000195431, REVEL 0.28, MetaLR 0.47, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- A5E (p.Ala5Glu), gnomAD 3-10141861-C-A, REVEL 0.31, MetaLR 0.52
- A5A (p.Ala5Ala), rs1355874307, gnomAD 3-10141862-G-A, CADD 10.60
- E6* (p.Glu6Ter), rs545406510, ClinGen CA351747032, ClinVar RCV001369118, ClinVar RCV004006817, AlphaMissense 0.10, MetaLR 0.33, Uncertain significance
- E6A (p.Glu6Ala), rs1696114029, ClinGen CA351747033, ClinVar RCV001071455, ClinVar RCV004950253, AlphaMissense 0.15, MetaLR 0.30, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- E6D (p.Glu6Asp), rs1004620245, ClinGen CA16611153, ClinVar RCV000459599, ClinVar RCV002411515, REVEL 0.18, MetaLR 0.32, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- E6G (p.Glu6Gly), Ensembl rs1696114029, REVEL 0.20, AlphaMissense 0.15, Likely benign
- E6K (p.Glu6Lys), 1000Genomes rs545406510, ExAC rs545406510, gnomAD rs545406510, Likely benign, Hereditary cancer-predisposing syndrome
- E6Q (p.Glu6Gln), rs545406510, ClinGen CA351747031, ClinVar RCV002585053, ClinVar RCV004009443, REVEL 0.15, AlphaMissense 0.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- E6V (p.Glu6Val), Ensembl rs1696114029, REVEL 0.20, AlphaMissense 0.15, Likely benign
- N7D (p.Asn7Asp), Civic 849, cosmic curated COSV56571, gnomAD rs1311403806, REVEL 0.25, MetaLR 0.28, Pathogenic
- N7I (p.Asn7Ile), rs1575920892, ClinGen CA351747050, ClinVar RCV001046537, Ensembl rs1575920892, AlphaMissense 0.12, MetaLR 0.36, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- N7K (p.Asn7Lys), rs1060503561, ClinGen CA351747053, ClinVar RCV001053669, ClinVar RCV004678922, REVEL 0.14, MetaLR 0.29, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- N7S (p.Asn7Ser), rs1575920892, ClinGen CA351747048, ClinVar RCV001298878, ClinVar RCV002418901, REVEL 0.23, AlphaMissense 0.12, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- N7T (p.Asn7Thr), rs1575920892, ClinGen CA351747046, cosmic curated COSV56571, ClinVar RCV000812261, AlphaMissense 0.12, MetaLR 0.36, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- N7N (p.Asn7Asn), rs1060503561, gnomAD 3-10141868-C-T, CADD 5.82
- W8* (p.Trp8Ter), rs1060503551, ClinGen CA16611056, ClinVar RCV000458561, Ensembl rs1060503551, AlphaMissense 0.09, MetaLR 0.32, Uncertain significance
- W8C (p.Trp8Cys), Ensembl rs2125124441, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- W8G (p.Trp8Gly), rs1352171735, ClinGen CA351747059, ClinVar RCV002042393, ClinVar RCV003230725, REVEL 0.24, MetaLR 0.34, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Pheochromoc
- W8L (p.Trp8Leu), rs1060503551, ClinGen CA351747063, ClinVar RCV001205122, Ensembl rs1060503551, REVEL 0.18, AlphaMissense 0.09, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- W8R (p.Trp8Arg), rs1352171735, ClinGen CA351747057, ClinVar RCV000559388, ClinVar RCV003478129, REVEL 0.24, MetaLR 0.34, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia; not provided
- D9A (p.Asp9Ala), rs1060503560, ClinGen CA16611161, ClinVar RCV000471735, ClinVar RCV002436462, AlphaMissense 0.07, MetaLR 0.32, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- D9E (p.Asp9Glu), rs1017141110, ClinGen CA16611250, ClinVar RCV000456617, ClinVar RCV002436463, REVEL 0.13, MetaLR 0.24, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- D9G (p.Asp9Gly), rs1060503560, ClinGen CA351747074, ClinVar RCV001913314, Ensembl rs1060503560, REVEL 0.21, AlphaMissense 0.07, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- D9H (p.Asp9His), rs587780730, ClinGen CA351747072, ClinVar RCV000807206, ClinVar RCV003362960, REVEL 0.25, MetaLR 0.38, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- D9N (p.Asp9Asn), rs587780730, ClinGen CA020190, ClinVar RCV000123104, ClinVar RCV000524493, REVEL 0.17, MetaLR 0.36, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- D9V (p.Asp9Val), rs1060503560, ClinGen CA351747079, ClinVar RCV002658864, ClinVar RCV004066811, REVEL 0.20, AlphaMissense 0.07, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- D9Y (p.Asp9Tyr), ExAC rs587780730, TOPMed rs587780730, gnomAD rs587780730, REVEL 0.23, MetaLR 0.35, Likely benign
- D9D (p.Asp9Asp), rs1017141110, gnomAD 3-10141874-C-T, CADD 5.72
- E10* (p.Glu10Ter), rs1057519261, ClinGen CA351747089, ClinVar RCV000662559, ClinVar RCV001372824, CADD 33.00, Likely benign
- E10A (p.Glu10Ala), rs786204065, ClinGen CA351747093, ClinVar RCV003789849, ClinVar RCV004005999, AlphaMissense 0.12, MetaLR 0.33, Uncertain significance, Von Hippel-Lindau syndrome; Hereditary cancer-predisposing syndrome; Chuvash pol
- E10D (p.Glu10Asp), rs963501454, ClinGen CA70042189, ClinVar RCV000821203, ClinVar RCV001018646, AlphaMissense 0.09, MetaLR 0.36, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- E10G (p.Glu10Gly), rs786204065, ClinGen CA351747095, cosmic curated COSV56568, ClinVar RCV001302369, REVEL 0.12, AlphaMissense 0.12, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- E10K (p.Glu10Lys), rs1057519261, ClinGen CA16043991, cosmic curated COSV56546, ClinVar RCV000415643, REVEL 0.29, MetaLR 0.34, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Nonpapillary renal cell carcin
- E10Q (p.Glu10Gln), rs1057519261, ClinGen CA351747087, ClinVar RCV001345999, ClinVar RCV002438799, REVEL 0.24, MetaLR 0.42, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- E10V (p.Glu10Val), rs786204065, ClinGen CA020251, ClinVar RCV000167948, ClinVar RCV003462253, REVEL 0.27, AlphaMissense 0.12, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- E10E (p.Glu10Glu), rs963501454, gnomAD 3-10141877-G-A, AlphaMissense 0.09, MetaLR 0.36
- A11D (p.Ala11Asp), Ensembl rs2125124474, REVEL 0.31, MetaLR 0.41, Uncertain significance
- A11G (p.Ala11Gly), Ensembl rs2125124474, REVEL 0.19, MetaLR 0.35, Uncertain significance, Pheochromocytoma; Nonpapillary renal cell carcinoma; Chuvash polycythemia
- A11P (p.Ala11Pro), rs1236604706, ClinGen CA351747101, ClinVar RCV000554589, ClinVar RCV000764457, REVEL 0.32, AlphaMissense 0.11, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- A11S (p.Ala11Ser), rs1236604706, ClinGen CA351747111, ClinVar RCV001890358, ClinVar RCV004693865, AlphaMissense 0.11, MetaLR 0.42, Uncertain significance, not provided; Chuvash polycythemia; Von Hippel-Lindau syndrome
- A11V (p.Ala11Val), Ensembl rs2125124474, REVEL 0.25, MetaLR 0.41, Uncertain significance
- A11A (p.Ala11Ala), rs778674343, gnomAD 3-10141880-C-T, CADD 5.51
- E12* (p.Glu12Ter), rs1064794788, ClinGen CA351747132, ClinVar RCV002465984, ClinVar RCV004007469, CADD 33.00, Uncertain significance
- E12D (p.Glu12Asp), rs973493604, ClinGen CA16617780, ClinVar RCV000483032, ClinVar RCV000538470, REVEL 0.18, MetaLR 0.34, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- E12G (p.Glu12Gly), rs1380706798, ClinGen CA351747137, ClinVar RCV001364592, ClinVar RCV004951619, AlphaMissense 0.08, MetaLR 0.36, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; not provided
- E12K (p.Glu12Lys), cosmic curated COSV56550, 1000Genomes rs1064794788, TOPMed rs1064794788, gnomAD rs1064794788, REVEL 0.35, MetaLR 0.36, Uncertain significance
- E12L (p.Glu12Leu), rs1696115662, ClinGen CA1139655721, ClinVar RCV001206074, ClinVar RCV001586049, Uncertain significance, Chuvash polycythemia; not provided; Von Hippel-Lindau syndrome
- E12Q (p.Glu12Gln), rs1064794788, ClinGen CA16617779, ClinVar RCV000485486, ClinVar RCV000808373, REVEL 0.21, MetaLR 0.43, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- E12V (p.Glu12Val), rs1380706798, ClinGen CA351747133, ClinVar RCV004016206, TOPMed rs1380706798, REVEL 0.21, AlphaMissense 0.08, Uncertain significance, Von Hippel-Lindau syndrome
- E12A (p.Glu12Ala), gnomAD 3-10141882-A-C, REVEL 0.15, MetaLR 0.33
- V13E (p.Val13Glu), TOPMed rs1553619289, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- V13G (p.Val13Gly), rs1553619289, ClinGen CA351747163, ClinVar RCV000631277, ClinVar RCV002358759, REVEL 0.25, MetaLR 0.28, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- V13I (p.Val13Ile), rs919338576, ClinGen CA70042199, ClinVar RCV000532105, ClinVar RCV004023757, REVEL 0.24, AlphaMissense 0.11, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- V13L (p.Val13Leu), rs919338576, ClinGen CA351747145, ClinVar RCV001927607, ClinVar RCV004804288, AlphaMissense 0.11, MetaLR 0.35, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- V13A (p.Val13Ala), rs1553619289, ClinGen CA351747150, ClinVar RCV001210678, ClinVar RCV002356899, REVEL 0.22, MetaLR 0.19, Conflicting interpretations, Von Hippel-Lindau syndrome; Hereditary cancer-predisposing syndrome; Chuvash pol
- V13V (p.Val13Val), rs996469746, gnomAD 3-10141886-A-T, CADD 1.57
- G14C (p.Gly14Cys), gnomAD rs1060503559, REVEL 0.42, MetaLR 0.61, Uncertain significance
- G14D (p.Gly14Asp), rs1575921044, ClinGen CA351747177, cosmic curated COSV99846, ClinVar RCV000798642, AlphaMissense 0.10, MetaLR 0.56, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- G14R (p.Gly14Arg), rs1060503559, ClinGen CA16611166, ClinVar RCV000467814, ClinVar RCV002475889, REVEL 0.39, MetaLR 0.61, Uncertain significance, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- G14S (p.Gly14Ser), rs1060503559, ClinGen CA351747168, ClinVar RCV001316987, ClinVar RCV001569177, REVEL 0.21, MetaLR 0.55, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Chuvash polycythemia
- G14V (p.Gly14Val), gnomAD 3-10141888-G-T, REVEL 0.40, MetaLR 0.56
- G14G (p.Gly14Gly), gnomAD 3-10141889-C-A, CADD 5.54
- A15G (p.Ala15Gly), gnomAD rs1159027899, Uncertain significance
- A15P (p.Ala15Pro), Ensembl rs1060503568, Uncertain significance
- A15T (p.Ala15Thr), rs1060503568, ClinGen CA16611060, ClinVar RCV000457623, ClinVar RCV002329080, REVEL 0.08, MetaLR 0.34, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- A15V (p.Ala15Val), rs1159027899, ClinGen CA351747200, ClinVar RCV003786268, ClinVar RCV004950674, REVEL 0.17, MetaLR 0.37, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- A15S (p.Ala15Ser), gnomAD 3-10141890-G-T, REVEL 0.07, MetaLR 0.35
- A15E (p.Ala15Glu), gnomAD 3-10141891-C-A, REVEL 0.33, MetaLR 0.36
- A15A (p.Ala15Ala), rs563813895, gnomAD 3-10141892-G-A, CADD 4.11
- E16* (p.Glu16Ter), rs1060503556, ClinGen CA351747213, ClinVar RCV000559942, ClinVar RCV001022924, CADD 34.00, Uncertain significance
- E16A (p.Glu16Ala), rs864622379, ClinGen CA348482, ClinVar RCV000204236, ClinVar RCV000662539, REVEL 0.33, MetaLR 0.46, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- E16D (p.Glu16Asp), rs1057522140, ClinGen CA351747226, ClinVar RCV000631257, ClinVar RCV003362869, AlphaMissense 0.11, MetaLR 0.46, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- E16G (p.Glu16Gly), TOPMed rs864622379, REVEL 0.33, MetaLR 0.47, Uncertain significance
- E16K (p.Glu16Lys), gnomAD rs1060503556, REVEL 0.41, MetaLR 0.47, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; Von Hippel-Lindau syndro
- E16Q (p.Glu16Gln), rs1060503556, ClinGen CA16611058, ClinVar RCV000460356, ClinVar RCV002329079, REVEL 0.24, MetaLR 0.48, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- E16V (p.Glu16Val), rs864622379, ClinGen CA351747220, ClinVar RCV001023076, ClinVar RCV003769571, REVEL 0.39, MetaLR 0.48, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- E16E (p.Glu16Glu), rs1057522140, gnomAD 3-10141895-G-A, AlphaMissense 0.11, MetaLR 0.46
- E17* (p.Glu17Ter), rs1028898216, ClinGen CA70042221, cosmic curated COSV10455, ClinVar RCV000657735, AlphaMissense 0.13, MetaLR 0.57, Uncertain significance
- E17D (p.Glu17Asp), rs2125124538, ClinGen CA351747262, ClinVar RCV001360453, ClinVar RCV001773713, AlphaMissense 0.10, MetaLR 0.54, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- E17G (p.Glu17Gly), Ensembl rs2125124533
- E17K (p.Glu17Lys), rs1028898216, ClinGen CA351747236, ClinVar RCV002039677, TOPMed rs1028898216, AlphaMissense 0.13, MetaLR 0.57, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- E17V (p.Glu17Val), Ensembl rs2125124533
- E17A (p.Glu17Ala), gnomAD 3-10141897-A-C, REVEL 0.33, MetaLR 0.56
- A18E (p.Ala18Glu), TOPMed rs1553619302, REVEL 0.27, AlphaMissense 0.09, Uncertain significance
- A18G (p.Ala18Gly), rs1553619302, ClinGen CA351747279, ClinVar RCV004520907, TOPMed rs1553619302, AlphaMissense 0.09, MetaLR 0.34, Likely benign, Hereditary cancer-predisposing syndrome
- A18S (p.Ala18Ser), rs1332272921, ClinGen CA351747273, ClinVar RCV000563088, gnomAD rs1332272921, REVEL 0.20, MetaLR 0.35, Likely benign, Hereditary cancer-predisposing syndrome
- A18T (p.Ala18Thr), gnomAD rs1332272921, REVEL 0.19, MetaLR 0.35, Uncertain significance
- A18V (p.Ala18Val), rs1553619302, ClinGen CA351747282, ClinVar RCV000527264, ClinVar RCV002350176, REVEL 0.17, AlphaMissense 0.09, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- p.Ala18 Glu37del, gnomAD 3-10141886-AGGCGC, CADD 14.00
- A18A (p.Ala18Ala), rs1305687580, gnomAD 3-10141901-A-C, CADD 7.88
- G19D (p.Gly19Asp), Ensembl rs2125124549, Uncertain significance, Hereditary cancer-predisposing syndrome
- G19R (p.Gly19Arg), rs1382387188, ClinGen CA351747289, ClinVar RCV001966298, gnomAD rs1382387188, AlphaMissense 0.09, MetaLR 0.36, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- G19S (p.Gly19Ser), gnomAD rs1382387188, REVEL 0.15, AlphaMissense 0.09, Uncertain significance
- G19V (p.Gly19Val), rs2125124549, ClinGen CA351747296, ClinVar RCV001969825, ClinVar RCV003892994, REVEL 0.17, MetaLR 0.33, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- G19G (p.Gly19Gly), rs1453582828, gnomAD 3-10141904-C-A, CADD 7.42
- V20A (p.Val20Ala), rs929332564, ClinGen CA70042225, ClinVar RCV001047363, ClinVar RCV002355024, REVEL 0.19, AlphaMissense 0.08, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- V20D (p.Val20Asp), rs929332564, ClinGen CA351747322, ClinVar RCV002025581, ClinVar RCV005772327, AlphaMissense 0.08, MetaLR 0.29, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- V20F (p.Val20Phe), Ensembl rs2125124555, REVEL 0.17, AlphaMissense 0.09, Uncertain significance
- V20G (p.Val20Gly), Ensembl rs929332564, Likely benign
- V20I (p.Val20Ile), cosmic curated COSV99847, Ensembl rs2125124555, REVEL 0.11, AlphaMissense 0.09, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- V20L (p.Val20Leu), rs2125124555, ClinGen CA351747312, ClinVar RCV002299580, Ensembl rs2125124555, AlphaMissense 0.09, MetaLR 0.28, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- V20S (p.Val20Ser), rs1553619308, gnomAD 3-10141903-GC-G, CADD 19.70
- V20V (p.Val20Val), rs1553619311, gnomAD 3-10141907-C-T, CADD 3.77
- E21* (p.Glu21Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E21A (p.Glu21Ala), rs1060503548, ClinGen CA16611259, ClinVar RCV000476242, ClinVar RCV001025102, REVEL 0.29, AlphaMissense 0.10, Uncertain significance, not provided; Von Hippel-Lindau syndrome; Chuvash polycythemia
- E21G (p.Glu21Gly), rs1060503548, ClinGen CA351747347, ClinVar RCV003306571, AlphaMissense 0.10, MetaLR 0.34, Uncertain significance, Hereditary cancer-predisposing syndrome
- E21K (p.Glu21Lys), rs2125124562, ClinGen CA351747330, cosmic curated COSV10956, ClinVar RCV002015601, REVEL 0.38, AlphaMissense 0.12, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome; Hereditary cancer-predisposing
- E21Q (p.Glu21Gln), rs2125124562, ClinGen CA351747333, ClinVar RCV003779423, ClinVar RCV006292462, AlphaMissense 0.12, MetaLR 0.29, Uncertain significance, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- E21V (p.Glu21Val), rs1060503548, ClinGen CA351747354, ClinVar RCV000818167, TOPMed rs1060503548, AlphaMissense 0.10, MetaLR 0.34, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- E22* (p.Glu22Ter), NCI-TCGA Cosmic COSV5656, Variant assessed as somatic; high impact.
- E22D (p.Glu22Asp), Ensembl rs768452685, REVEL 0.26, MetaLR 0.52, Likely benign
- E22G (p.Glu22Gly), rs2125124570, ClinGen CA351747380, ClinVar RCV001898786, ClinVar RCV002361206, REVEL 0.30, AlphaMissense 0.08, Uncertain significance, not specified; not provided; Von Hippel-Lindau syndrome
- E22K (p.Glu22Lys), rs1696118115, ClinGen CA351747372, cosmic curated COSV56568, ClinVar RCV001344937, REVEL 0.24, MetaLR 0.51, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- E22V (p.Glu22Val), rs2125124570, ClinGen CA351747381, ClinVar RCV003360626, AlphaMissense 0.08, MetaLR 0.54, Uncertain significance, Hereditary cancer-predisposing syndrome
- E22E (p.Glu22Glu), rs768452685, gnomAD 3-10141913-G-A, CADD 7.47
- Y23* (p.Tyr23Ter), rs1553619313, TOPMed rs1553619313, ClinGen CA351747398, cosmic curated COSV56552, CADD 33.00, Likely benign
- Y23C (p.Tyr23Cys), rs2125124577, ClinGen CA351747392, ClinVar RCV003808349, Ensembl rs2125124577, AlphaMissense 0.08, MetaLR 0.31, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- Y23D (p.Tyr23Asp), rs1696118253, ClinGen CA351747388, ClinVar RCV002001124, ClinVar RCV004946996, AlphaMissense 0.09, MetaLR 0.33, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia; Pheochromocytoma
- Y23H (p.Tyr23His), rs1696118253, ClinGen CA351747387, ClinVar RCV001891842, Ensembl rs1696118253, REVEL 0.20, AlphaMissense 0.09, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- Y23N (p.Tyr23Asn), rs1696118253, ClinGen CA351747386, ClinVar RCV003815467, Ensembl rs1696118253, AlphaMissense 0.09, MetaLR 0.33, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia
- Y23S (p.Tyr23Ser), Ensembl rs2125124577, Uncertain significance
- Y23Y (p.Tyr23Tyr), rs1553619313, gnomAD 3-10141916-C-T, CADD 4.85
- G24A (p.Gly24Ala), TOPMed rs878854129, gnomAD rs878854129, Uncertain significance
- G24C (p.Gly24Cys), rs1438223626, ClinGen CA351747408, ClinVar RCV000699569, ClinVar RCV001026041, REVEL 0.34, MetaLR 0.47, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Pheochromocytoma
- G24D (p.Gly24Asp), rs878854129, ClinGen CA10582111, ClinVar RCV000231328, ClinVar RCV000412262, REVEL 0.35, MetaLR 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- G24R (p.Gly24Arg), rs1438223626, ClinGen CA351747414, ClinVar RCV001874775, ClinVar RCV003164225, REVEL 0.33, MetaLR 0.45, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- G24S (p.Gly24Ser), rs1438223626, ClinGen CA351747411, ClinVar RCV000803089, ClinVar RCV003153844, REVEL 0.07, MetaLR 0.32, Conflicting interpretations, Chuvash polycythemia; Von Hippel-Lindau syndrome; Ovarian cancer
- G24V (p.Gly24Val), rs878854129, ClinGen CA351747418, ClinVar RCV002028247, TOPMed rs878854129, REVEL 0.31, MetaLR 0.34, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- G24G (p.Gly24Gly), rs1375079282, gnomAD 3-10141919-C-A, CADD 6.06
- P25A (p.Pro25Ala), rs745338799, ClinGen CA042053, ClinVar RCV000465780, ClinVar RCV002383832, REVEL 0.15, MetaLR 0.34, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; Von Hippel-Lindau syndro
- P25H (p.Pro25His), 1000Genomes rs35460768, ESP rs35460768, ExAC rs35460768, TOPMed rs35460768, REVEL 0.27, MetaLR 0.46, Benign, in PCC
- P25L (p.Pro25Leu), rs35460768, Civic 850, ClinGen CA020538, cosmic curated COSV56547, REVEL 0.15, MetaLR 0.35, Benign, Von Hippel-Lindau syndrome
- P25R (p.Pro25Arg), 1000Genomes rs35460768, ESP rs35460768, ExAC rs35460768, TOPMed rs35460768, REVEL 0.28, MetaLR 0.35, Uncertain significance, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- P25S (p.Pro25Ser), cosmic curated COSV56571, ExAC rs745338799, TOPMed rs745338799, gnomAD rs745338799, REVEL 0.12, MetaLR 0.35, Uncertain significance, in PCC
- P25P (p.Pro25Pro), rs1553619317, gnomAD 3-10141922-T-C, CADD 7.17
- E26G (p.Glu26Gly), rs2125124609, ClinGen CA351747453, cosmic curated COSV56572, ClinVar RCV002603364, AlphaMissense 0.14, MetaLR 0.34, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- E26K (p.Glu26Lys), rs1575921209, ClinGen CA351747440, cosmic curated COSV56572, ClinVar RCV001026731, AlphaMissense 0.10, MetaLR 0.32, Uncertain significance, Hereditary cancer-predisposing syndrome
- E26Q (p.Glu26Gln), rs1575921209, ClinGen CA351747441, ClinVar RCV003806296, ClinVar RCV004950696, AlphaMissense 0.10, MetaLR 0.32, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- E26V (p.Glu26Val), Ensembl rs2125124609, Uncertain significance
- E26A (p.Glu26Ala), gnomAD 3-10141924-A-C, REVEL 0.35, MetaLR 0.28
- E27A (p.Glu27Ala), rs2125124617, ClinGen CA351747474, ClinVar RCV004008235, ClinVar RCV004573451, AlphaMissense 0.07, MetaLR 0.34, Uncertain significance, Von Hippel-Lindau syndrome; Chuvash polycythemia; Nonpapillary renal cell carcin
- E27D (p.Glu27Asp), rs2125124618, Ensembl rs2125124618, ClinGen CA351747482, ClinVar RCV002427900, AlphaMissense 0.10, MetaLR 0.35, Uncertain significance, Hereditary cancer-predisposing syndrome; Chuvash polycythemia; Von Hippel-Lindau
- E27G (p.Glu27Gly), rs2125124617, ClinGen CA351747476, ClinVar RCV002019164, ClinVar RCV002423183, REVEL 0.15, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Von Hippel-Lindau syndrome; Chuvash pol
- E27K (p.Glu27Lys), Ensembl rs2125124614
- E27Q (p.Glu27Gln), Ensembl rs2125124614
- D28A (p.Asp28Ala), Ensembl rs2125124629, Likely benign
- D28G (p.Asp28Gly), rs2125124629, ClinGen CA351747510, cosmic curated COSV56543, ClinVar RCV002248933, AlphaMissense 0.05, MetaLR 0.24, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified
- D28N (p.Asp28Asn), rs1553619319, ClinGen CA351747487, cosmic curated COSV56555, ClinVar RCV000561967, REVEL 0.18, AlphaMissense 0.07, Conflicting interpretations, Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing
- D28V (p.Asp28Val), rs2125124629, ClinGen CA351747502, cosmic curated COSV56570, ClinVar RCV001910005, AlphaMissense 0.05, MetaLR 0.24, Uncertain significance, Chuvash polycythemia; Von Hippel-Lindau syndrome
- D28E (p.Asp28Glu), gnomAD rs1198287627, REVEL 0.24, MetaLR 0.36, Uncertain significance, not provided
Public VHL analysis runs
- VHL analysis run — VHL (1,319 variants) — completed 2026-08-10