SOS1 (Son of sevenless homolog 1) variants and mutations
SOS1 (also known as Son of sevenless homolog 1) is a human protein-coding gene encoding a son of sevenless homolog 1 protein. It activates RAS by exchanging GDP for GTP downstream of receptor tyrosine kinases. Germline activating variants are a common cause of Noonan syndrome, while excessive SOS1-RAS signaling can contribute to cancer. This analysis covers 2,058 SOS1 variants and mutations. Of these, 70% have computational variant effect predictions. Disease context includes Noonan syndrome, hereditary gingival fibromatosis, and RASopathy. Example SOS1 variants include Q2*, Q2E, and Q2H.
Variant analysis overview
- Gene: SOS1
- Protein: Son of sevenless homolog 1
- UniProt accession: Q07889
- Organism: Homo sapiens
- Variants analyzed: 2058
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,792 unspecified-consequence records; 3 stop lost; 1 stop retained variant; 92 synonymous variants; 131 missense variants; 16 frameshift variants; 1 splice-region variants; 5 stop-gained variants; 1 in-frame insertions; 11 in-frame deletions; 5 substitution
- Prediction scores: 1,440 variants have prediction scores (70% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Noonan syndrome, hereditary gingival fibromatosis, RASopathy, cancer, Noonan syndrome and Noonan-related syndrome, Abnormality of the cardiovascular system, bone development disease, Noonan syndrome 3, hypertensive disorder, endometrial cancer, skin basal cell carcinoma, endometrial endometrioid adenocarcinoma.
Protein structure and variant hotspots
- Protein features: 4 domains; 8 post-translational modification sites.
- Structural context: 799 variants have structural context.
- PTM context: 16 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable SOS1 variants
Examples include Q2*, Q2E, Q2H, Q2K, Q2L, Q2P, A3S, A3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- Q2* (p.Gln2Ter), ExAC rs587781174, gnomAD rs587781174, CADD 39.00, Uncertain significance
- Q2E (p.Gln2Glu), ExAC rs587781174, gnomAD rs587781174, REVEL 0.30, CADD 23.90, Uncertain significance
- Q2H (p.Gln2His), gnomAD rs1673827939, REVEL 0.30, CADD 25.40
- Q2K (p.Gln2Lys), rs587781174, ClinGen CA346374816, ClinVar RCV002254876, ClinVar RCV003539415, REVEL 0.31, CADD 24.20, Uncertain significance, RASopathy; Noonan syndrome
- Q2L (p.Gln2Leu), rs886056026, ClinGen CA10615444, ClinVar RCV000330632, ClinVar RCV000389511, REVEL 0.33, CADD 24.20, Uncertain significance, Fibromatosis, gingival, 1; Noonan syndrome 4; Cardiovascular phenotype
- Q2P (p.Gln2Pro), Ensembl rs886056026, REVEL 0.47, CADD 26.10, Uncertain significance
- A3S (p.Ala3Ser), rs533757634, ClinGen CA1624907, ClinVar RCV001913952, ClinVar RCV002423053, REVEL 0.21, CADD 21.30, Conflicting interpretations, Cardiovascular phenotype; not provided; RASopathy
- A3V (p.Ala3Val), rs745455374, ClinGen CA1624906, ClinVar RCV003654741, ExAC rs745455374, REVEL 0.29, CADD 23.10, Uncertain significance, RASopathy
- Q4R (p.Gln4Arg), rs770627276, ClinGen CA1624904, ClinVar RCV003655833, ExAC rs770627276, REVEL 0.24, CADD 19.10, Uncertain significance, RASopathy
- L6P (p.Leu6Pro), rs749077460, ClinGen CA1624903, ClinVar RCV002971331, ClinVar RCV003274107, REVEL 0.30, CADD 23.80, Conflicting interpretations, RASopathy; not specified; Cardiovascular phenotype
- P7L (p.Pro7Leu), rs755983212, ClinGen CA1624901, ClinVar RCV002972559, ClinVar RCV005433944, REVEL 0.15, CADD 22.70, Conflicting interpretations, not specified; RASopathy; Cardiovascular phenotype
- P7S (p.Pro7Ser), NCI-TCGA TCGA novel, REVEL 0.20, CADD 21.00, Variant assessed as somatic; moderate impact.
- Y8C (p.Tyr8Cys), rs781093356, ClinGen CA1624900, ClinVar RCV001898444, ExAC rs781093356, REVEL 0.72, CADD 29.20, Uncertain significance, RASopathy
- Y8F (p.Tyr8Phe), rs781093356, ClinGen CA346374768, ClinVar RCV001331442, ClinVar RCV001863242, REVEL 0.55, CADD 24.20, Uncertain significance, Noonan syndrome 4; Fibromatosis, gingival, 1; RASopathy
- Y8H (p.Tyr8His), Ensembl rs1673826865, REVEL 0.66, CADD 28.50, Uncertain significance, not provided
- E9D (p.Glu9Asp), gnomAD rs765768180, REVEL 0.15, CADD 15.30, Likely benign
- E9K (p.Glu9Lys), rs1347187972, ClinGen CA346374765, ClinVar RCV000680743, ClinVar RCV002493123, REVEL 0.34, CADD 24.50, Uncertain significance, not provided; Fibromatosis, gingival, 1; Noonan syndrome 4
- E9Q (p.Glu9Gln), TOPMed rs1347187972, Uncertain significance
- E9V (p.Glu9Val), rs2465606490, ClinGen CA346374762, ClinVar RCV002437382, Uncertain significance, Cardiovascular phenotype
- F10V (p.Phe10Val), rs2148243308, ClinGen CA346374749, ClinVar RCV002005559, Ensembl rs2148243308, REVEL 0.56, CADD 24.40, Uncertain significance, RASopathy
- F11L (p.Phe11Leu), rs1673826225, ClinGen CA346374725, ClinVar RCV001058145, Ensembl rs1673826225, REVEL 0.28, CADD 23.00, Uncertain significance, RASopathy
- S12C (p.Ser12Cys), rs751776207, ClinGen CA346374720, ClinVar RCV001327635, ClinVar RCV005601755, REVEL 0.36, CADD 26.30, Uncertain significance, RASopathy; Noonan syndrome 4
- S12G (p.Ser12Gly), rs751776207, ClinGen CA1624898, ClinVar RCV003068725, ClinVar RCV003491220, REVEL 0.29, CADD 22.50, Uncertain significance, not specified; RASopathy
- S12R (p.Ser12Arg), gnomAD rs1454378065, REVEL 0.38, CADD 25.20, Uncertain significance, Cardiovascular phenotype
- E13G (p.Glu13Gly), rs2148243276, ClinGen CA346374704, ClinVar RCV001543121, ClinVar RCV002032544, REVEL 0.46, CADD 23.50, Uncertain significance, RASopathy; not provided; Fibromatosis, gingival, 1
- E13K (p.Glu13Lys), cosmic curated COSV67676, REVEL 0.37, CADD 23.40
- E13Q (p.Glu13Gln), rs766698773, ClinGen CA1624897, ClinVar RCV002731327, ExAC rs766698773, REVEL 0.28, CADD 22.80, Uncertain significance, RASopathy
- E14* (p.Glu14Ter), rs2148243262, ClinGen CA346374693, ClinVar RCV002267519, Ensembl rs2148243262, CADD 38.00, Uncertain significance
- E14G (p.Glu14Gly), ExAC rs750790046, gnomAD rs750790046, REVEL 0.64, CADD 32.00
- E14K (p.Glu14Lys), rs2148243262, ClinGen CA346374696, ClinVar RCV002323331, ClinVar RCV003655364, Uncertain significance, Cardiovascular phenotype; RASopathy
- E14Q (p.Glu14Gln), cosmic curated COSV10121
- N15K (p.Asn15Lys), ExAC rs765652390, TOPMed rs765652390, gnomAD rs765652390, REVEL 0.41, CADD 23.50
- P17H (p.Pro17His), cosmic curated COSV10121
- K18M (p.Lys18Met), ExAC rs777196517, gnomAD rs777196517, REVEL 0.68, CADD 27.70
- K18N (p.Lys18Asn), rs2465606345, ClinGen CA346374635, ClinVar RCV003832305, Uncertain significance, RASopathy
- K18R (p.Lys18Arg), ExAC rs777196517, gnomAD rs777196517, REVEL 0.33, CADD 23.00
- G21E (p.Gly21Glu), TOPMed rs1673825085
- G21R (p.Gly21Arg), rs771423136, ClinGen CA346374606, ClinVar RCV001347175, ExAC rs771423136, REVEL 0.68, CADD 23.90, Uncertain significance, RASopathy
- L22V (p.Leu22Val), rs773916713, ClinGen CA1624890, cosmic curated COSV67674, ClinVar RCV003655455, REVEL 0.26, CADD 18.60, Conflicting interpretations, Cardiovascular phenotype; RASopathy
- L23P (p.Leu23Pro), cosmic curated COSV67675, REVEL 0.81, CADD 27.90
- V24E (p.Val24Glu), cosmic curated COSV67673, REVEL 0.63, CADD 24.20
- V24L (p.Val24Leu), rs1673824599, ClinGen CA346374579, ClinVar RCV003283414, ClinVar RCV003655419, REVEL 0.34, CADD 22.50, Uncertain significance, RASopathy; Cardiovascular phenotype
- P25S (p.Pro25Ser), rs139592595, ClinGen CA181527, ClinVar RCV000154848, ClinVar RCV000521504, REVEL 0.21, CADD 20.30, Benign, RASopathy
- A26S (p.Ala26Ser), rs1303622703, ClinGen CA346374563, ClinVar RCV003540053, ClinVar RCV004369199, REVEL 0.17, CADD 19.00, Uncertain significance, Cardiovascular phenotype; RASopathy
- A26T (p.Ala26Thr), TOPMed rs1303622703, gnomAD rs1303622703, REVEL 0.43, CADD 24.20, Uncertain significance
- K28R (p.Lys28Arg), rs1057517867, ClinGen CA16042460, ClinVar RCV000413861, Ensembl rs1057517867, REVEL 0.17, CADD 17.70, Uncertain significance, not specified
- K29T (p.Lys29Thr), rs2465606172, ClinGen CA346374541, ClinVar RCV003655560, REVEL 0.60, CADD 27.60, Uncertain significance, RASopathy
- G32E (p.Gly32Glu), cosmic curated COSV10593
- G32R (p.Gly32Arg), rs764501046, ClinGen CA1624858, ClinVar RCV003540349, ClinVar RCV004992671, REVEL 0.22, CADD 21.00, Conflicting interpretations, Cardiovascular phenotype; RASopathy
- H35R (p.His35Arg), rs886041928, ClinGen CA10602879, ClinVar RCV000384120, Ensembl rs886041928, AlphaMissense 0.99, MetaLR 0.77, Uncertain significance, not provided
- P36L (p.Pro36Leu), rs2148140667, ClinGen CA346374328, ClinVar RCV001763286, Ensembl rs2148140667, AlphaMissense 0.59, MetaLR 0.92, Uncertain significance, not provided
- T37A (p.Thr37Ala), rs150565592, ClinGen CA136074, ClinVar RCV000038509, ClinVar RCV000159147, REVEL 0.23, CADD 19.00, Likely benign, RASopathy
- T37I (p.Thr37Ile), gnomAD rs1295255931, REVEL 0.36, CADD 22.10, Uncertain significance, not specified; RASopathy; Cardiovascular phenotype
- T37N (p.Thr37Asn), cosmic curated COSV10972
- L38F (p.Leu38Phe), cosmic curated COSV67675, gnomAD rs1242664084, REVEL 0.68, CADD 24.40
- E39* (p.Glu39Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E39K (p.Glu39Lys), rs375934353, ClinGen CA1624856, cosmic curated COSV67673, ClinVar RCV000681137, REVEL 0.22, CADD 20.20, Conflicting interpretations, not provided; RASopathy; Cardiovascular phenotype
- E39V (p.Glu39Val), rs1391761076, ClinGen CA346374310, ClinVar RCV002601393, ClinVar RCV003289541, REVEL 0.18, CADD 22.50, Conflicting interpretations, RASopathy; Cardiovascular phenotype
- N41D (p.Asn41Asp), cosmic curated COSV67673, REVEL 0.20, CADD 20.40
- D42H (p.Asp42His), NCI-TCGA Cosmic COSV6767, cosmic curated COSV67675, Variant assessed as somatic; moderate impact.
- D42N (p.Asp42Asn), rs1402273679, ClinGen CA346374293, ClinVar RCV000812614, gnomAD rs1402273679, REVEL 0.31, CADD 23.70, Uncertain significance, RASopathy
- D42V (p.Asp42Val), gnomAD rs1329027771, REVEL 0.64, CADD 24.30
- D43H (p.Asp43His), rs730881052, ClinGen CA297289, ClinVar RCV000159184, ClinVar RCV002467501, REVEL 0.62, CADD 26.10, Uncertain significance, Cardiovascular phenotype; not provided; RASopathy
- A44G (p.Ala44Gly), Ensembl rs2148140603
- A44T (p.Ala44Thr), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10121, Variant assessed as somatic; moderate impact.
- Q46L (p.Gln46Leu), rs1190714377, ClinGen CA346374261, ClinVar RCV002264902, gnomAD rs1190714377, AlphaMissense 0.10, MetaLR 0.48, Uncertain significance, Noonan syndrome 4
- Q46R (p.Gln46Arg), gnomAD rs1190714377, REVEL 0.54, AlphaMissense 0.10, Uncertain significance
- Y47H (p.Tyr47His), TOPMed rs1418446263, gnomAD rs1418446263, REVEL 0.70, CADD 22.70
- V48A (p.Val48Ala), rs373898570, ClinGen CA234979, cosmic curated COSV10121, ClinVar RCV000153987, REVEL 0.76, CADD 25.50, Uncertain significance
- V48D (p.Val48Asp), cosmic curated COSV10470
- V48I (p.Val48Ile), ExAC rs764909346, gnomAD rs764909346, REVEL 0.30, CADD 15.60
- E50* (p.Glu50Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E50K (p.Glu50Lys), rs2148140584, ClinGen CA346374238, ClinVar RCV002014303, Ensembl rs2148140584, AlphaMissense 0.43, MetaLR 0.55, Uncertain significance, RASopathy
- L51S (p.Leu51Ser), gnomAD rs1458813036, REVEL 0.93, CADD 27.10
- L53S (p.Leu53Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L53V (p.Leu53Val), rs2465395423, ClinGen CA346374216, ClinVar RCV003984956, Uncertain significance, Noonan syndrome 4
- Q54H (p.Gln54His), ExAC rs763520126, TOPMed rs763520126, gnomAD rs763520126, REVEL 0.52, CADD 5.28, Uncertain significance, SOS1-related disorder
- N57I (p.Asn57Ile), Ensembl rs1671637125
- N57S (p.Asn57Ser), Ensembl rs1671637125
- N57Y (p.Asn57Tyr), rs765764610, ClinGen CA46014818, ClinVar RCV001050512, ClinVar RCV002245843, REVEL 0.53, CADD 22.80, Uncertain significance, Fibromatosis, gingival, 1; Noonan syndrome 4; Cardiovascular phenotype
- M58T (p.Met58Thr), ExAC rs746906388, gnomAD rs746906388
- M58V (p.Met58Val), rs2148140531, ClinGen CA346374180, cosmic curated COSV67675, ClinVar RCV001911324, AlphaMissense 0.18, MetaLR 0.50, Uncertain significance, RASopathy; Cardiovascular phenotype
- L59I (p.Leu59Ile), TOPMed rs1442738935, gnomAD rs1442738935, REVEL 0.69, CADD 23.20
- Q61H (p.Gln61His), rs1355644577, ClinGen CA346374154, ClinVar RCV001761139, gnomAD rs1355644577, REVEL 0.49, CADD 20.20, Uncertain significance, not provided
- Q61L (p.Gln61Leu), rs1671636707, ClinGen CA346374155, ClinVar RCV001316022, Ensembl rs1671636707, AlphaMissense 0.11, MetaLR 0.40, Uncertain significance, RASopathy
- Q63E (p.Gln63Glu), cosmic curated COSV10824
- Q63L (p.Gln63Leu), rs557722218, ClinGen CA1624849, ClinVar RCV003091826, 1000Genomes rs557722218, REVEL 0.53, CADD 24.00, Likely benign, RASopathy
- P64L (p.Pro64Leu), rs1671636391, ClinGen CA346374134, ClinVar RCV002410671, ClinVar RCV003100936, REVEL 0.77, CADD 26.90, Uncertain significance, RASopathy; Cardiovascular phenotype
- R65* (p.Arg65Ter), gnomAD rs1303674298, CADD 37.00
- R65G (p.Arg65Gly), cosmic curated COSV10470
- R65Q (p.Arg65Gln), NCI-TCGA TCGA novel, REVEL 0.44, CADD 24.50, Uncertain significance, RASopathy
- S66G (p.Ser66Gly), rs2465395173, ClinGen CA346374127, ClinVar RCV003333637, REVEL 0.43, CADD 23.60, Uncertain significance, Noonan syndrome 4
- S66R (p.Ser66Arg), rs1221581719, ClinGen CA346374121, ClinVar RCV003654784, ClinVar RCV004593444, REVEL 0.51, CADD 24.50, Uncertain significance, RASopathy; not provided
- A67T (p.Ala67Thr), rs730881053, ClinGen CA297295, ClinVar RCV000159186, ClinVar RCV001309736, REVEL 0.29, CADD 22.00, Conflicting interpretations, Cardiovascular phenotype; not provided; Noonan syndrome 4
- A67V (p.Ala67Val), gnomAD rs1445719629, REVEL 0.21, CADD 16.30
- D69A (p.Asp69Ala), Ensembl rs1558497933, REVEL 0.82, CADD 27.30
- D69E (p.Asp69Glu), rs2465395089, ClinGen CA346374103, ClinVar RCV002422299, REVEL 0.60, CADD 23.30, Uncertain significance, Cardiovascular phenotype
- D69H (p.Asp69His), rs771172095, ClinGen CA1624848, ClinVar RCV002421956, ClinVar RCV003098587, REVEL 0.76, CADD 26.20, Uncertain significance, RASopathy; not provided; Cardiovascular phenotype
- D69N (p.Asp69Asn), ExAC rs771172095, gnomAD rs771172095, REVEL 0.66, CADD 26.70, Uncertain significance, not provided; Cardiovascular phenotype; RASopathy
- V70L (p.Val70Leu), gnomAD rs1671635364, REVEL 0.67, CADD 24.60
- E71Q (p.Glu71Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R73C (p.Arg73Cys), cosmic curated COSV10972, ExAC rs772133124, TOPMed rs772133124, gnomAD rs772133124, REVEL 0.71, CADD 32.00, Likely benign, RASopathy
- R73H (p.Arg73His), NCI-TCGA Cosmic COSV1012, TOPMed rs1671301694, Variant assessed as somatic; moderate impact.
- R73P (p.Arg73Pro), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10121, Variant assessed as somatic; moderate impact.
- V74I (p.Val74Ile), rs1292587800, ClinGen CA346374056, ClinVar RCV000681438, gnomAD rs1292587800, AlphaMissense 0.22, MetaLR 0.73, Uncertain significance, not provided
- V74L (p.Val74Leu), gnomAD rs1292587800, REVEL 0.63, AlphaMissense 0.22, Uncertain significance
- Q75L (p.Gln75Leu), rs786205522, ClinGen CA236037, ClinVar RCV000171289, Ensembl rs786205522, AlphaMissense 0.17, MetaLR 0.58, Likely pathogenic, not provided
- Q75R (p.Gln75Arg), rs786205522, ClinGen CA346374046, ClinVar RCV002791766, AlphaMissense 0.17, MetaLR 0.58, Uncertain significance, RASopathy
- S77K (p.Ser77Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- F78C (p.Phe78Cys), rs201352584, ClinGen CA297244, cosmic curated COSV10593, ClinVar RCV000460292, REVEL 0.86, CADD 29.70, Conflicting interpretations, SOS1-related disorder; Ventricular tachycardia; not provided
- F78I (p.Phe78Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P79A (p.Pro79Ala), TOPMed rs1671301191, gnomAD rs1671301191, REVEL 0.69, CADD 23.70
- P79R (p.Pro79Arg), gnomAD rs1217237678, REVEL 0.72, CADD 26.70
- H80R (p.His80Arg), NCI-TCGA Cosmic COSV6767, cosmic curated COSV67677, Variant assessed as somatic; moderate impact.
- P81S (p.Pro81Ser), Ensembl rs1170908990
- I82T (p.Ile82Thr), rs1278714177, ClinGen CA346373997, ClinVar RCV003060992, TOPMed rs1278714177, REVEL 0.82, CADD 25.90, Uncertain significance, RASopathy
- I82V (p.Ile82Val), rs397517157, ClinGen CA136101, ClinVar RCV000038533, ClinVar RCV000541335, REVEL 0.42, CADD 24.30, Conflicting interpretations, Cardiovascular phenotype; not specified; not provided
- D83A (p.Asp83Ala), ExAC rs749485750, gnomAD rs749485750, REVEL 0.86, CADD 27.10
- D83G (p.Asp83Gly), ExAC rs749485750, gnomAD rs749485750, REVEL 0.88, CADD 27.60
- D83N (p.Asp83Asn), gnomAD rs1401325594, REVEL 0.60, CADD 24.50
- D83Y (p.Asp83Tyr), cosmic curated COSV67675
- K84E (p.Lys84Glu), TOPMed rs1319777416, REVEL 0.65, CADD 23.10
- W85* (p.Trp85Ter), NCI-TCGA Cosmic COSV6767, cosmic curated COSV67675, Variant assessed as somatic; high impact.
- W85C (p.Trp85Cys), rs2465361618, ClinGen CA346373974, ClinVar RCV003043174, Likely pathogenic, RASopathy
- W85G (p.Trp85Gly), gnomAD rs730881054, Pathogenic
- W85R (p.Trp85Arg), rs730881054, ClinGen CA346373979, ClinVar RCV000545153, ClinVar RCV001261068, AlphaMissense 1.00, MetaLR 0.76, Pathogenic/Likely pathogenic, RASopathy; Noonan syndrome 4; Fibromatosis, gingival, 1
- A86T (p.Ala86Thr), rs2465361612, ClinGen CA346373971, ClinVar RCV003080280, cosmic curated COSV10121, Uncertain significance, RASopathy
- I87K (p.Ile87Lys), cosmic curated COSV67674
- A88D (p.Ala88Asp), rs2465361577, ClinGen CA346373955, ClinVar RCV002428624, Uncertain significance, Cardiovascular phenotype
- D89A (p.Asp89Ala), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10121, Variant assessed as somatic; moderate impact.
- D89E (p.Asp89Glu), rs2124610871, ClinGen CA346373946, ClinVar RCV001966375, Ensembl rs2124610871, AlphaMissense 0.85, MetaLR 0.62, Uncertain significance, RASopathy
- D89N (p.Asp89Asn), cosmic curated COSV67675
- A90T (p.Ala90Thr), NCI-TCGA Cosmic COSV6767, cosmic curated COSV67677, Variant assessed as somatic; moderate impact.
- A90V (p.Ala90Val), rs2465361545, ClinGen CA346373941, ClinVar RCV002428985, NCI-TCGA Cosmic COSV1012, Uncertain significance, Cardiovascular phenotype
- Q91E (p.Gln91Glu), cosmic curated COSV10470
- S92P (p.Ser92Pro), cosmic curated COSV10121
- A93D (p.Ala93Asp), NCI-TCGA Cosmic COSV6767, cosmic curated COSV67677, Variant assessed as somatic; moderate impact.
- I94T (p.Ile94Thr), rs397517161, ClinGen CA136114, ClinVar RCV000038539, ClinVar RCV002467547, REVEL 0.76, CADD 25.30, Uncertain significance, not specified; Noonan syndrome 4; Fibromatosis, gingival, 1
- I94V (p.Ile94Val), rs144757941, ClinGen CA1624825, ClinVar RCV000523770, ClinVar RCV000761049, REVEL 0.43, CADD 19.40, Likely benign, RASopathy
- E95K (p.Glu95Lys), rs1558493384, ClinGen CA346373912, ClinVar RCV000702580, Ensembl rs1558493384, AlphaMissense 0.82, MetaLR 0.77, Uncertain significance, RASopathy
- E95Q (p.Glu95Gln), rs1558493384, ClinGen CA346373913, ClinVar RCV002705596, AlphaMissense 0.82, MetaLR 0.77, Uncertain significance, RASopathy
- K96N (p.Lys96Asn), cosmic curated COSV10611
- R97G (p.Arg97Gly), rs2465361297, ClinGen CA346373897, ClinVar RCV002438010, ClinVar RCV002473386, REVEL 0.23, CADD 22.10, Uncertain significance, not provided; Cardiovascular phenotype
- K98R (p.Lys98Arg), ExAC rs770048860, gnomAD rs770048860
- R99* (p.Arg99Ter), cosmic curated COSV10655
- R100I (p.Arg100Ile), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10121, Variant assessed as somatic; moderate impact.
- N101H (p.Asn101His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N101K (p.Asn101Lys), ESP rs138764039, ExAC rs138764039, TOPMed rs138764039, gnomAD rs138764039, Likely benign
- N101S (p.Asn101Ser), ExAC rs781600559
- N101T (p.Asn101Thr), cosmic curated COSV10972
- P102L (p.Pro102Leu), rs1553362937, ClinGen CA346373861, ClinVar RCV003335797, cosmic curated COSV10533, REVEL 0.71, AlphaMissense 0.74, Likely pathogenic, Noonan syndrome 4
- P102R (p.Pro102Arg), rs1553362937, ClinGen CA346373860, NCI-TCGA Cosmic COSV6767, cosmic curated COSV67676, AlphaMissense 0.74, MetaLR 0.71, Pathogenic/Likely pathogenic, RASopathy; not provided; Noonan syndrome 4
- P102S (p.Pro102Ser), TOPMed rs1671299094
- P102T (p.Pro102Thr), TOPMed rs1671299094
- L103S (p.Leu103Ser), gnomAD rs1188721742, REVEL 0.96, CADD 27.30
- S104C (p.Ser104Cys), ExAC rs752017140, TOPMed rs752017140, gnomAD rs752017140, REVEL 0.24, CADD 23.10, Uncertain significance, Noonan syndrome 4; Cardiovascular phenotype
- S104F (p.Ser104Phe), ExAC rs752017140, TOPMed rs752017140, gnomAD rs752017140, REVEL 0.13, CADD 21.00
- S104Y (p.Ser104Tyr), rs752017140, ClinGen CA346373848, ClinVar RCV003655828, REVEL 0.14, CADD 20.40, Uncertain significance, RASopathy
- L105F (p.Leu105Phe), rs1230538285, ClinGen CA346373844, ClinVar RCV002590259, AlphaMissense 0.71, MetaLR 0.75, Uncertain significance, RASopathy
- L105I (p.Leu105Ile), TOPMed rs1230538285, gnomAD rs1230538285, REVEL 0.51, AlphaMissense 0.71
- V107I (p.Val107Ile), rs1235907251, ClinGen CA346373834, ClinVar RCV002322943, AlphaMissense 0.56, MetaLR 0.45, Uncertain significance, Cardiovascular phenotype
- V107L (p.Val107Leu), gnomAD rs1235907251, REVEL 0.32, AlphaMissense 0.56
- E108G (p.Glu108Gly), rs886041923, ClinGen CA10602855, ClinVar RCV000265265, ClinVar RCV002321944, REVEL 0.56, AlphaMissense 0.93, Conflicting interpretations, Cardiovascular phenotype; not provided
- E108K (p.Glu108Lys), rs397517164, ClinGen CA261739, cosmic curated COSV67677, ClinVar RCV000038546, AlphaMissense 0.96, MetaLR 0.55, Pathogenic, Noonan syndrome
- E108V (p.Glu108Val), rs886041923, ClinGen CA346373825, ClinVar RCV001311921, Ensembl rs886041923, AlphaMissense 0.93, MetaLR 0.57, Likely pathogenic, not provided
- I110L (p.Ile110Leu), cosmic curated COSV10443
- I110N (p.Ile110Asn), rs2465361100, ClinGen CA346373811, ClinVar RCV002944092, NCI-TCGA TCGA novel, Uncertain significance, RASopathy
- I110V (p.Ile110Val), rs1276127499, ClinGen CA346373813, ClinVar RCV001508986, ClinVar RCV002568001, AlphaMissense 0.28, MetaLR 0.20, Uncertain significance, Cardiovascular phenotype; RASopathy; not provided
- H111R (p.His111Arg), rs1572860651, ClinGen CA346373803, ClinVar RCV000807098, Ensembl rs1572860651, AlphaMissense 0.99, MetaLR 0.77, Uncertain significance, RASopathy
- P112R (p.Pro112Arg), rs397517166, ClinGen CA261741, cosmic curated COSV67674, ClinVar RCV000038549, REVEL 0.35, CADD 23.90, Conflicting interpretations, RASopathy; Noonan syndrome
- P112S (p.Pro112Ser), cosmic curated COSV10750
- L113F (p.Leu113Phe), cosmic curated COSV10121
- L113S (p.Leu113Ser), rs2465361064, ClinGen CA346373791, ClinVar RCV003021819, Uncertain significance, RASopathy
- E116G (p.Glu116Gly), cosmic curated COSV10470, REVEL 0.90, CADD 33.00
- E116K (p.Glu116Lys), rs747505741, ClinVar RCV004701957, AlphaMissense 0.84, MetaLR 0.64, Uncertain significance, not provided
- E116Q (p.Glu116Gln), ExAC rs747505741, REVEL 0.69, AlphaMissense 0.84, Uncertain significance, RASopathy
- E116V (p.Glu116Val), rs2124607524, ClinGen CA346373752, ClinVar RCV002005302, Ensembl rs2124607524, AlphaMissense 0.86, MetaLR 0.74, Uncertain significance, RASopathy
- V117A (p.Val117Ala), cosmic curated COSV67675
- V117G (p.Val117Gly), rs201085754, ClinGen CA136140, ClinVar RCV000038552, ClinVar RCV000520887, REVEL 0.73, CADD 27.80, Likely benign, RASopathy
- V117L (p.Val117Leu), ExAC rs780406547, gnomAD rs780406547, Uncertain significance, Cardiovascular phenotype; RASopathy
Public SOS1 analysis runs
- SOS1 analysis run — SOS1 (2,058 variants) — completed 2026-08-18