SOS2 (Son of sevenless homolog 2) variants and mutations
SOS2 (also known as Son of sevenless homolog 2) is a human protein-coding gene encoding a son of sevenless homolog 2 protein. It activates RAS by catalyzing GDP-GTP exchange downstream of growth-factor receptors. Germline activating variants cause Noonan syndrome, generally through increased RAS-MAPK signaling. This analysis covers 1,818 SOS2 variants and mutations. Of these, 88% have computational variant effect predictions. Disease context includes Noonan syndrome, Noonan syndrome 9, and hypertensive disorder. Example SOS2 variants include M1T, Q2L, and A4S.
Variant analysis overview
- Gene: SOS2
- Protein: Son of sevenless homolog 2
- UniProt accession: Q07890
- Organism: Homo sapiens
- Variants analyzed: 1818
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,516 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 95 synonymous variants; 23 frameshift variants; 161 missense variants; 8 in-frame deletions; 4 in-frame insertions; 6 stop-gained variants; 2 splice-region variants; 1 substitution
- Prediction scores: 1,591 variants have prediction scores (88% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Noonan syndrome, Noonan syndrome 9, hypertensive disorder, essential hypertension, gout, RASopathy, kidney failure, Increased blood pressure, cardiovascular disorder, open-angle glaucoma, hydrops fetalis, type 2 diabetes mellitus.
Protein structure and variant hotspots
- Protein features: 4 domains; 1 post-translational modification sites.
- Structural context: 696 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 SOS2 variants
Examples include M1T, Q2L, A4S, P5A, Q6*, P7R, P7S, P7T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs2503347343, ClinGen CA389657765, ClinVar RCV003592744, Uncertain significance, Noonan syndrome 9
- Q2L (p.Gln2Leu), rs2503347322, ClinGen CA389657731, ClinVar RCV004517240, Uncertain significance, Cardiovascular phenotype
- A4S (p.Ala4Ser), TOPMed rs1441953271, gnomAD rs1441953271, REVEL 0.21, MetaLR 0.25, Uncertain significance, Noonan syndrome 9
- P5A (p.Pro5Ala), rs976486198, ClinGen CA260740027, ClinVar RCV001261117, ClinVar RCV001880004, REVEL 0.23, MetaLR 0.26, Conflicting interpretations, Noonan syndrome 9; Cardiovascular phenotype
- Q6* (p.Gln6Ter), rs2503347249, ClinVar RCV004593530, CADD 37.00, Uncertain significance
- P7R (p.Pro7Arg), rs755419078, ClinGen CA7177663, ClinVar RCV003756542, ExAC rs755419078, REVEL 0.17, MetaLR 0.39, Likely benign, Noonan syndrome 9
- P7S (p.Pro7Ser), cosmic curated COSV53568, TOPMed rs1887536522, REVEL 0.23, MetaLR 0.40, Uncertain significance, Noonan syndrome 9
- P7T (p.Pro7Thr), rs1887536522, ClinGen CA389657658, ClinVar RCV003755831, REVEL 0.20, MetaLR 0.37, Uncertain significance, Noonan syndrome 9
- E9G (p.Glu9Gly), rs2503347123, ClinGen CA389657626, ClinVar RCV003991600, REVEL 0.41, MetaLR 0.42, Likely pathogenic, Male infertility due to gonadal dysgenesis or sperm disorder
- E9K (p.Glu9Lys), cosmic curated COSV10724, ExAC rs751814626, gnomAD rs751814626, REVEL 0.39, MetaLR 0.38
- E9Q (p.Glu9Gln), ExAC rs751814626, gnomAD rs751814626, REVEL 0.29, MetaLR 0.42
- F11C (p.Phe11Cys), NCI-TCGA TCGA novel, MetaLR 0.49, MetaSVM -0.20, Variant assessed as somatic; moderate impact.
- F11L (p.Phe11Leu), gnomAD rs1221101657, REVEL 0.30, MetaLR 0.41
- F11Y (p.Phe11Tyr), rs2503347084, ClinGen CA389657596, ClinVar RCV002454687, REVEL 0.23, MetaLR 0.33, Uncertain significance, Cardiovascular phenotype
- S12C (p.Ser12Cys), 1000Genomes rs201495842, REVEL 0.40, MetaLR 0.51
- E13G (p.Glu13Gly), ExAC rs758896322, gnomAD rs758896322, REVEL 0.31, MetaLR 0.51
- E13K (p.Glu13Lys), rs1887535959, ClinGen CA389657569, cosmic curated COSV10724, ClinVar RCV004517239, REVEL 0.34, MetaLR 0.50, Uncertain significance, Cardiovascular phenotype
- E14D (p.Glu14Asp), rs2503346950, ClinGen CA389657541, ClinVar RCV003066958, REVEL 0.39, MetaLR 0.51, Uncertain significance, Noonan syndrome 9
- E14K (p.Glu14Lys), rs2503346981, ClinGen CA389657556, ClinVar RCV002323328, REVEL 0.57, MetaLR 0.58, Uncertain significance, Cardiovascular phenotype
- S16T (p.Ser16Thr), TOPMed rs1364159457, gnomAD rs1364159457, MetaLR 0.41, MetaSVM -0.50, Likely benign, Noonan syndrome 9
- P17A (p.Pro17Ala), ExAC rs750929787, gnomAD rs750929787, REVEL 0.18, MetaLR 0.28, Uncertain significance
- P17L (p.Pro17Leu), rs1015229594, ClinGen CA260740003, ClinVar RCV004154054, TOPMed rs1015229594, REVEL 0.16, MetaLR 0.32, Uncertain significance, Cardiovascular phenotype
- P17Q (p.Pro17Gln), TOPMed rs1015229594, gnomAD rs1015229594, REVEL 0.19, MetaLR 0.33, Uncertain significance
- P17R (p.Pro17Arg), TOPMed rs1015229594, gnomAD rs1015229594, REVEL 0.16, MetaLR 0.34, Uncertain significance
- P17S (p.Pro17Ser), rs750929787, ClinGen CA389657520, ClinVar RCV001925067, ExAC rs750929787, REVEL 0.17, MetaLR 0.35, Uncertain significance, Noonan syndrome 9
- R20Q (p.Arg20Gln), TOPMed rs1436943286, REVEL 0.53, MetaLR 0.52
- R20W (p.Arg20Trp), NCI-TCGA TCGA novel, REVEL 0.75, MetaLR 0.57, Variant assessed as somatic; moderate impact.
- L22V (p.Leu22Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L23F (p.Leu23Phe), rs1003888969, ClinGen CA260739996, ClinVar RCV003592856, 1000Genomes rs1003888969, REVEL 0.20, MetaLR 0.25, Uncertain significance, Noonan syndrome 9
- V24D (p.Val24Asp), ExAC rs764249804, gnomAD rs764249804, REVEL 0.62, MetaLR 0.52
- V24F (p.Val24Phe), rs2503346760, ClinGen CA389657476, ClinVar RCV002367364, ClinVar RCV004774673, REVEL 0.65, MetaLR 0.63, Uncertain significance, Cardiovascular phenotype; not provided
- S25L (p.Ser25Leu), rs1887534256, ClinGen CA389657468, ClinVar RCV001813717, TOPMed rs1887534256, REVEL 0.26, MetaLR 0.31, Uncertain significance, Noonan syndrome and Noonan-related syndrome
- A26T (p.Ala26Thr), gnomAD rs1453155265, REVEL 0.56, MetaLR 0.57
- R28G (p.Arg28Gly), rs2503346594, ClinGen CA389657455, ClinVar RCV004517244, REVEL 0.51, MetaLR 0.43, Uncertain significance, Cardiovascular phenotype
- R28Q (p.Arg28Gln), rs1887533896, ClinGen CA389657450, ClinVar RCV002434902, ClinVar RCV003591946, REVEL 0.49, MetaLR 0.49, Uncertain significance, Noonan syndrome 9; Cardiovascular phenotype
- V30F (p.Val30Phe), rs758144954, ExAC rs758144954, gnomAD rs758144954, REVEL 0.74, MetaLR 0.77, Variant assessed as somatic; moderate impact.
- Q31R (p.Gln31Arg), Ensembl rs2139796369, REVEL 0.49, MetaLR 0.69
- E32K (p.Glu32Lys), rs1461064079, ClinGen CA389651564, ClinVar RCV002374132, gnomAD rs1461064079, REVEL 0.22, MetaLR 0.39, Uncertain significance, Cardiovascular phenotype
- P36A (p.Pro36Ala), rs2503209915, ClinGen CA389651496, ClinVar RCV003756430, REVEL 0.83, MetaLR 0.88, Uncertain significance, Noonan syndrome 9
- P36L (p.Pro36Leu), gnomAD rs1276710063, REVEL 0.86, MetaLR 0.91, Uncertain significance, Cardiovascular phenotype
- T37I (p.Thr37Ile), rs370550495, ClinGen CA7177608, ClinVar RCV002428922, ClinVar RCV003102110, REVEL 0.29, MetaLR 0.44, Conflicting interpretations, Noonan syndrome 9; Cardiovascular phenotype
- T37S (p.Thr37Ser), TOPMed rs1886596399, MetaLR 0.30, MetaSVM -0.92
- S39T (p.Ser39Thr), rs2139796314, ClinGen CA389651456, ClinVar RCV001879005, Ensembl rs2139796314, REVEL 0.20, MetaLR 0.30, Uncertain significance, Noonan syndrome 9
- N41D (p.Asn41Asp), rs575983927, ClinGen CA7177606, ClinVar RCV001952667, ClinVar RCV004041990, REVEL 0.24, MetaLR 0.28, Conflicting interpretations, Noonan syndrome 9; Cardiovascular phenotype
- N41S (p.Asn41Ser), rs1249312381, ClinGen CA389651419, ClinVar RCV002367239, ClinVar RCV003754952, REVEL 0.32, MetaLR 0.22, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- E43V (p.Glu43Val), Ensembl rs1886595959, REVEL 0.68, MetaLR 0.56
- S44P (p.Ser44Pro), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99365, REVEL 0.57, MetaLR 0.44, Variant assessed as somatic; moderate impact.
- L45F (p.Leu45Phe), TOPMed rs1886595894, Uncertain significance, Noonan syndrome 9
- Y46C (p.Tyr46Cys), rs1162838729, ClinGen CA7177603, ClinVar RCV003009152, TOPMed rs1162838729, REVEL 0.26, MetaLR 0.36, Uncertain significance, Noonan syndrome 9
- Y46S (p.Tyr46Ser), rs1162838729, ClinGen CA389651335, ClinVar RCV002027305, TOPMed rs1162838729, Uncertain significance, Noonan syndrome 9
- I48T (p.Ile48Thr), 1000Genomes rs556194352, TOPMed rs556194352, REVEL 0.85, MetaLR 0.60, Uncertain significance, Cardiovascular phenotype
- I48V (p.Ile48Val), rs763552267, ClinGen CA7177602, ClinVar RCV000366863, ClinVar RCV003422189, REVEL 0.30, MetaLR 0.21, Conflicting interpretations, SOS2-related disorder; Noonan syndrome 9; not provided
- E49* (p.Glu49Ter), NCI-TCGA Cosmic COSV5357, cosmic curated COSV53575, Variant assessed as somatic; high impact.
- E50K (p.Glu50Lys), cosmic curated COSV10724, ExAC rs775028449, gnomAD rs775028449, REVEL 0.34, MetaLR 0.48
- I52S (p.Ile52Ser), ExAC rs771695525, gnomAD rs771695525, REVEL 0.86, MetaLR 0.74
- F53S (p.Phe53Ser), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99366, MetaLR 0.39, MetaSVM -0.15, Variant assessed as somatic; moderate impact.
- Q54R (p.Gln54Arg), Ensembl rs1886595184
- L55P (p.Leu55Pro), rs2139796125, ClinGen CA389651188, ClinVar RCV002227673, Ensembl rs2139796125, Uncertain significance, Noonan syndrome 9
- L55V (p.Leu55Val), Ensembl rs1886595109, REVEL 0.74, MetaLR 0.67
- L56F (p.Leu56Phe), rs2503209483, ClinGen CA389651184, ClinVar RCV003592154, REVEL 0.72, MetaLR 0.72, Uncertain significance, Noonan syndrome 9
- K58E (p.Lys58Glu), rs2139796115, ClinGen CA389651150, ClinVar RCV002033111, Ensembl rs2139796115, Uncertain significance, Noonan syndrome 9
- C60* (p.Cys60Ter), NCI-TCGA Cosmic COSV5357, cosmic curated COSV53570, Variant assessed as somatic; high impact.
- C60F (p.Cys60Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C60W (p.Cys60Trp), ExAC rs759897386, gnomAD rs759897386, MetaLR 0.77, MetaSVM 0.70
- M61I (p.Met61Ile), gnomAD rs1402287989, REVEL 0.23, MetaLR 0.22
- M61L (p.Met61Leu), rs774761716, ClinGen CA389651103, ClinVar RCV002410320, REVEL 0.25, MetaLR 0.28, Uncertain significance, Cardiovascular phenotype
- M61V (p.Met61Val), rs774761716, ClinGen CA7177597, ClinVar RCV001948308, ClinVar RCV002407101, REVEL 0.21, MetaLR 0.27, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- A62T (p.Ala62Thr), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99365, Variant assessed as somatic; moderate impact.
- A62V (p.Ala62Val), rs1886594687, ClinGen CA389651075, ClinVar RCV001240821, ClinVar RCV004994363, REVEL 0.34, MetaLR 0.57, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- Q63H (p.Gln63His), rs771269309, ClinGen CA7177596, ClinVar RCV001174628, ClinVar RCV002411671, REVEL 0.49, MetaLR 0.45, Uncertain significance, Noonan syndrome 9; not specified; Cardiovascular phenotype
- R65K (p.Arg65Lys), rs2503209313, ClinGen CA389651031, ClinVar RCV004364016, Uncertain significance, Cardiovascular phenotype
- T66I (p.Thr66Ile), gnomAD rs1886594420, REVEL 0.61, MetaLR 0.70
- V67L (p.Val67Leu), gnomAD rs1418008191, REVEL 0.45, MetaLR 0.52
- Q68E (p.Gln68Glu), gnomAD rs1382054541, REVEL 0.42, MetaLR 0.58, Likely benign, Noonan syndrome 9
- Q68R (p.Gln68Arg), rs2503209228, ClinGen CA389650984, ClinVar RCV004517228, Uncertain significance, Cardiovascular phenotype
- D69N (p.Asp69Asn), rs2503209200, ClinGen CA389650977, ClinVar RCV003592654, REVEL 0.64, MetaLR 0.78, Uncertain significance, Noonan syndrome 9
- V70I (p.Val70Ile), gnomAD rs1179049396, REVEL 0.45, MetaLR 0.68
- V70L (p.Val70Leu), gnomAD rs1179049396, REVEL 0.66, MetaLR 0.73, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- E71Q (p.Glu71Gln), rs1566478915, NCI-TCGA Cosmic COSV5356, cosmic curated COSV53564, Ensembl rs1566478915, REVEL 0.62, MetaLR 0.77, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- E72A (p.Glu72Ala), Ensembl rs1886471144, REVEL 0.58, MetaLR 0.62, Uncertain significance, Cardiovascular phenotype
- E72G (p.Glu72Gly), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99365, REVEL 0.65, MetaLR 0.59, Variant assessed as somatic; moderate impact.
- E72K (p.Glu72Lys), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99366, Uncertain significance, Noonan syndrome 9
- E72Q (p.Glu72Gln), Ensembl rs1886471225, MetaLR 0.35, MetaSVM -0.71
- R73* (p.Arg73Ter), TOPMed rs1475534419, CADD 37.00
- V74I (p.Val74Ile), rs1886470934, ClinGen CA389650417, ClinVar RCV001037486, Ensembl rs1886470934, Uncertain significance, Noonan syndrome 9
- Q75E (p.Gln75Glu), rs2503193935, ClinGen CA389650405, ClinVar RCV002843287, Uncertain significance, Noonan syndrome 9
- Q75R (p.Gln75Arg), rs2139783861, ClinGen CA389650399, ClinVar RCV001898247, Ensembl rs2139783861, Uncertain significance, Noonan syndrome 9
- T77I (p.Thr77Ile), 1000Genomes rs565261873, ExAC rs565261873, TOPMed rs565261873, gnomAD rs565261873, MetaLR 0.64, MetaSVM 0.35, Likely benign
- T77S (p.Thr77Ser), rs565261873, ClinGen CA7177575, ClinVar RCV001295786, ClinVar RCV005278795, REVEL 0.43, MetaLR 0.30, Conflicting interpretations, Cardiovascular phenotype; Noonan syndrome 9; not specified
- H80R (p.His80Arg), ExAC rs748602123, gnomAD rs748602123, REVEL 0.43, MetaLR 0.52
- H80Y (p.His80Tyr), rs2503193817, ClinGen CA389650334, ClinVar RCV003301375, Uncertain significance, Cardiovascular phenotype
- P81L (p.Pro81Leu), Ensembl rs1886470354
- P81S (p.Pro81Ser), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99366, MetaLR 0.78, MetaSVM 0.65, Variant assessed as somatic; moderate impact.
- I82V (p.Ile82Val), rs545263131, ClinGen CA7177573, ClinVar RCV001984338, ClinVar RCV002443015, REVEL 0.64, MetaLR 0.65, Uncertain significance, Noonan syndrome 9; SOS2-related disorder; Cardiovascular phenotype
- W85* (p.Trp85Ter), Ensembl rs1886469855
- A86V (p.Ala86Val), rs146272145, ClinGen CA7177572, ClinVar RCV000801445, ClinVar RCV002458466, REVEL 0.79, MetaLR 0.76, Conflicting interpretations, Cardiovascular phenotype; Noonan syndrome 9
- I87T (p.Ile87Thr), rs747274422, ClinGen CA7177571, ClinVar RCV002004015, ClinVar RCV002441198, REVEL 0.90, MetaLR 0.71, Uncertain significance, Noonan syndrome 9; Cardiovascular phenotype
- A88V (p.Ala88Val), rs2503193558, ClinGen CA389650209, ClinVar RCV003755697, Uncertain significance, Noonan syndrome 9
- D89G (p.Asp89Gly), ExAC rs780385201, gnomAD rs780385201, REVEL 0.84, MetaLR 0.71
- Q91L (p.Gln91Leu), Ensembl rs1566477467, REVEL 0.57, MetaLR 0.58
- Q91P (p.Gln91Pro), rs1566477467, ClinGen CA389650174, ClinVar RCV003755509, Uncertain significance, Noonan syndrome 9
- S92T (p.Ser92Thr), gnomAD rs1229207865
- S92Y (p.Ser92Tyr), TOPMed rs1886468962, gnomAD rs1886468962, REVEL 0.53, MetaLR 0.69
- I94M (p.Ile94Met), rs753611130, ClinGen CA7177568, ClinVar RCV002435074, ClinVar RCV006471342, REVEL 0.61, MetaLR 0.62, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- I94V (p.Ile94Val), rs2503193412, ClinGen CA389650108, ClinVar RCV003756280, REVEL 0.40, MetaLR 0.58, Uncertain significance, Noonan syndrome 9
- R97P (p.Arg97Pro), ExAC rs777574895, TOPMed rs777574895, gnomAD rs777574895, REVEL 0.53, MetaLR 0.37, Uncertain significance
- R97Q (p.Arg97Gln), rs777574895, ClinGen CA389650038, NCI-TCGA Cosmic COSV5357, cosmic curated COSV53572, REVEL 0.27, MetaLR 0.23, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- R99Q (p.Arg99Gln), rs369592322, ClinGen CA260722383, cosmic curated COSV53569, ClinVar RCV002023593, Uncertain significance, Noonan syndrome 9
- R100G (p.Arg100Gly), TOPMed rs112221991, REVEL 0.88, MetaLR 0.75
- R100I (p.Arg100Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R100K (p.Arg100Lys), gnomAD rs1298793905, MetaLR 0.75, MetaSVM 0.65, Uncertain significance, Noonan syndrome 9
- P102L (p.Pro102Leu), rs2503193225, ClinGen CA389649953, ClinVar RCV002444186, REVEL 0.59, MetaLR 0.56, Uncertain significance, Cardiovascular phenotype
- P102S (p.Pro102Ser), rs2139783538, ClinGen CA389649960, cosmic curated COSV53566, ClinVar RCV002000933, REVEL 0.51, MetaLR 0.50, Uncertain significance, Noonan syndrome 9
- L103V (p.Leu103Val), NCI-TCGA Cosmic COSV5356, Variant assessed as somatic; moderate impact.
- L104* (p.Leu104Ter), ExAC rs752560999
- P106L (p.Pro106Leu), TOPMed rs1886468088, MetaLR 0.94, MetaSVM 1.07
- D108E (p.Asp108Glu), rs754449669, ClinGen CA7177563, ClinVar RCV002638600, ExAC rs754449669, REVEL 0.31, MetaLR 0.23, Conflicting interpretations, Noonan syndrome 9; Cardiovascular phenotype
- D108N (p.Asp108Asn), rs1566477432, ClinGen CA389649875, ClinVar RCV000681069, ClinVar RCV003392517, Uncertain significance, SOS2-related disorder; not provided
- S113L (p.Ser113Leu), rs751240491, ClinGen CA7177562, NCI-TCGA Cosmic COSV9936, cosmic curated COSV99365, REVEL 0.17, MetaLR 0.04, Conflicting interpretations, Noonan syndrome 9; not specified; not provided
- K115R (p.Lys115Arg), rs2503192928, ClinGen CA389649821, ClinVar RCV003756196, Uncertain significance, Noonan syndrome 9
- E116K (p.Glu116Lys), rs2503186408, ClinGen CA389649805, ClinVar RCV003236176, Uncertain significance, not provided
- K121E (p.Lys121Glu), Ensembl rs2139779313
- K121R (p.Lys121Arg), rs1456011298, ClinGen CA389649766, ClinVar RCV001932681, TOPMed rs1456011298, REVEL 0.33, MetaLR 0.26, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- V122M (p.Val122Met), rs1208838203, ClinGen CA389649762, ClinVar RCV001307479, ClinVar RCV001813589, REVEL 0.48, MetaLR 0.44, Conflicting interpretations, Noonan syndrome and Noonan-related syndrome; Noonan syndrome 9; Cardiovascular p
- H125L (p.His125Leu), rs777300218, ClinGen CA7177534, ClinVar RCV001871005, ClinVar RCV002343932, REVEL 0.40, MetaLR 0.30, Conflicting interpretations, Cardiovascular phenotype; not specified; Noonan syndrome 9
- H125R (p.His125Arg), rs777300218, ClinGen CA389649737, ClinVar RCV002653646, ExAC rs777300218, REVEL 0.33, MetaLR 0.28, Uncertain significance, Noonan syndrome 9
- H125Y (p.His125Tyr), gnomAD rs1309867315, REVEL 0.47, MetaLR 0.42, Uncertain significance, Noonan syndrome 9; Cardiovascular phenotype
- S127F (p.Ser127Phe), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99366, MetaLR 0.53, MetaSVM 0.17, Variant assessed as somatic; moderate impact.
- L128Q (p.Leu128Gln), rs2503186072, ClinGen CA389649720, ClinVar RCV002355440, Uncertain significance, Cardiovascular phenotype
- L128V (p.Leu128Val), ExAC rs775777617, gnomAD rs775777617, REVEL 0.36, MetaLR 0.19
- I130M (p.Ile130Met), rs1886426829, ClinGen CA389649704, ClinVar RCV001299278, Ensembl rs1886426829, REVEL 0.33, MetaLR 0.19, Uncertain significance, Noonan syndrome 9
- I130V (p.Ile130Val), ExAC rs746148215, TOPMed rs746148215, REVEL 0.22, MetaLR 0.19, Uncertain significance, Cardiovascular phenotype
- V131L (p.Val131Leu), gnomAD rs1401319142, REVEL 0.43, MetaLR 0.34
- A132V (p.Ala132Val), rs2503185996, NCI-TCGA Cosmic COSV9936, cosmic curated COSV99366, ClinGen CA389649692, Uncertain significance, Noonan syndrome 9
- V133I (p.Val133Ile), gnomAD rs1464665792, REVEL 0.41, MetaLR 0.44
- E135Q (p.Glu135Gln), TOPMed rs1886426162, MetaLR 0.81, MetaSVM 0.65, Uncertain significance, Cardiovascular phenotype
- D140G (p.Asp140Gly), Ensembl rs1021775891
- D140H (p.Asp140His), NCI-TCGA Cosmic COSV5357, cosmic curated COSV53571, Variant assessed as somatic; moderate impact.
- I141T (p.Ile141Thr), rs1378958999, NCI-TCGA Cosmic COSV5357, cosmic curated COSV53573, gnomAD rs1378958999, REVEL 0.95, MetaLR 0.84, Variant assessed as somatic; moderate impact.
- L142F (p.Leu142Phe), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99366, Variant assessed as somatic; moderate impact.
- K143T (p.Lys143Thr), NCI-TCGA Cosmic COSV5356, NCI-TCGA Cosmic COSV5357, cosmic curated COSV53575, MetaLR 0.75, MetaSVM 0.67, Variant assessed as somatic; moderate impact.
- L144* (p.Leu144Ter), rs1886425451, ClinGen CA389649614, ClinVar RCV002628819, TOPMed rs1886425451, CADD 37.00, Uncertain significance
- A145V (p.Ala145Val), NCI-TCGA TCGA novel, MetaLR 0.49, MetaSVM -0.00, Variant assessed as somatic; moderate impact.
- G146S (p.Gly146Ser), TOPMed rs1886425211
- N147D (p.Asn147Asp), rs1435992315, ClinGen CA389649596, ClinVar RCV002333687, ClinVar RCV003591938, REVEL 0.70, MetaLR 0.75, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- V149I (p.Val149Ile), rs2503185700, ClinGen CA389649581, ClinVar RCV003324154, Uncertain significance, not specified
- F150S (p.Phe150Ser), rs1886424881, ClinGen CA389649571, ClinVar RCV001874570, Ensembl rs1886424881, REVEL 0.25, MetaLR 0.28, Uncertain significance, Noonan syndrome 9
- I152F (p.Ile152Phe), rs2503185669, ClinGen CA389649557, ClinVar RCV004093885, ClinVar RCV005099582, Uncertain significance, Cardiovascular phenotype; Noonan syndrome 9
- I152T (p.Ile152Thr), gnomAD rs1440645330, REVEL 0.78, MetaLR 0.43
- R153Q (p.Arg153Gln), rs779591050, ClinGen CA7177522, ClinVar RCV001302584, ExAC rs779591050, REVEL 0.51, MetaLR 0.40, Likely benign, Noonan syndrome 9
- R153W (p.Arg153Trp), Ensembl rs778339464, REVEL 0.74, MetaLR 0.48
- H154N (p.His154Asn), rs2503185591, ClinGen CA389649548, ClinVar RCV002296651, Uncertain significance, Noonan syndrome 9
- H154Q (p.His154Gln), rs528048319, ClinGen CA7177521, ClinVar RCV003880713, 1000Genomes rs528048319, REVEL 0.57, MetaLR 0.40, Uncertain significance, Noonan syndrome 9
- Y155C (p.Tyr155Cys), gnomAD rs1257223875, MetaLR 0.11, MetaSVM -0.98
- E156D (p.Glu156Asp), rs1886424066, ClinGen CA389649528, ClinVar RCV003854619, TOPMed rs1886424066, Uncertain significance, Noonan syndrome 9
- S158P (p.Ser158Pro), rs1210780288, ClinGen CA389649518, ClinVar RCV003076306, gnomAD rs1210780288, REVEL 0.54, MetaLR 0.36, Uncertain significance, Noonan syndrome 9
- Q159R (p.Gln159Arg), rs2503185500, ClinGen CA389649509, ClinVar RCV003031101, Uncertain significance, Noonan syndrome 9
- V164M (p.Val164Met), rs2503185417, ClinGen CA389649454, ClinVar RCV003756481, Uncertain significance, Noonan syndrome 9
- M166V (p.Met166Val), rs1555322175, ClinGen CA389649430, ClinVar RCV000521760, Ensembl rs1555322175, REVEL 0.51, MetaLR 0.26, Uncertain significance, Noonan syndrome 9
- C167F (p.Cys167Phe), gnomAD rs1283726128, REVEL 0.69, MetaLR 0.30, Uncertain significance
- C167Y (p.Cys167Tyr), rs1283726128, ClinGen CA389649409, ClinVar RCV001761092, gnomAD rs1283726128, Uncertain significance, not provided
- A168E (p.Ala168Glu), ExAC rs756399613, TOPMed rs756399613, gnomAD rs756399613, REVEL 0.87, MetaLR 0.75, Uncertain significance
- A168T (p.Ala168Thr), rs2139778845, ClinGen CA389649402, ClinVar RCV001360043, Ensembl rs2139778845, REVEL 0.84, MetaLR 0.75, Uncertain significance, Noonan syndrome 9
- A168V (p.Ala168Val), rs756399613, ClinGen CA7177520, NCI-TCGA Cosmic COSV5357, cosmic curated COSV53570, REVEL 0.76, MetaLR 0.66, Conflicting interpretations, Cardiovascular phenotype; Noonan syndrome 9
- D169E (p.Asp169Glu), rs2503185303, ClinGen CA389649380, ClinVar RCV002302128, REVEL 0.83, MetaLR 0.84, Uncertain significance, Noonan syndrome 9
- D169N (p.Asp169Asn), gnomAD rs1886422672, REVEL 0.77, MetaLR 0.86
- V171I (p.Val171Ile), rs1351192565, ClinGen CA389648380, ClinVar RCV003033556, gnomAD rs1351192565, REVEL 0.44, MetaLR 0.52, Uncertain significance, Noonan syndrome 9
- L172F (p.Leu172Phe), rs561507728, ClinGen CA389648368, ClinVar RCV001219555, TOPMed rs561507728, REVEL 0.55, MetaLR 0.73, Uncertain significance, Noonan syndrome 9
- M173V (p.Met173Val), NCI-TCGA Cosmic COSV5356, cosmic curated COSV53562, MetaLR 0.53, MetaSVM 0.01, Variant assessed as somatic; moderate impact.
- D174G (p.Asp174Gly), rs2139734704, ClinGen CA389648353, ClinVar RCV001752646, ClinVar RCV001868521, REVEL 0.86, MetaLR 0.54, Uncertain significance, not provided; Noonan syndrome 9
- M175L (p.Met175Leu), rs1336823806, ClinGen CA389648349, ClinVar RCV001299539, Ensembl rs1336823806, Uncertain significance, Noonan syndrome 9
- M175R (p.Met175Arg), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99366, Variant assessed as somatic; moderate impact.
- M175V (p.Met175Val), rs1336823806, ClinGen CA389648348, ClinVar RCV003394485, ClinVar RCV003592037, Uncertain significance, SOS2-related disorder; Noonan syndrome 9
- D177E (p.Asp177Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D177G (p.Asp177Gly), rs1313632636, ClinGen CA389648328, ClinVar RCV001261118, ClinVar RCV001563672, REVEL 0.46, MetaLR 0.36, Uncertain significance, Noonan syndrome 9
- D177V (p.Asp177Val), gnomAD rs1313632636, REVEL 0.70, MetaLR 0.38, Likely pathogenic, Noonan syndrome 9
- Q178* (p.Gln178Ter), rs770603835, ClinGen CA389648323, ClinVar RCV004100352, Likely benign
- Q178E (p.Gln178Glu), rs770603835, ClinGen CA7177508, ClinVar RCV001878761, ClinVar RCV002343934, REVEL 0.54, MetaLR 0.33, Conflicting interpretations, Noonan syndrome 9; Cardiovascular phenotype; not specified
- Q178H (p.Gln178His), rs2139734609, ClinGen CA389648318, ClinVar RCV001988284, Ensembl rs2139734609, REVEL 0.54, MetaLR 0.28, Uncertain significance, Noonan syndrome 9
- Q178P (p.Gln178Pro), rs1273376869, ClinGen CA389648322, ClinVar RCV000652819, ClinVar RCV004992447, REVEL 0.66, MetaLR 0.32, Uncertain significance, Noonan syndrome 9; Cardiovascular phenotype
Public SOS2 analysis runs
- SOS2 analysis run — SOS2 (1,818 variants) — completed 2026-08-19