SOS1 p.Val697=
c.2091A>T · rs1669533747 · VCV1648744
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Conditions
1
RASopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.036 | GERP -0.29, phastCons 0.89 |
| Overall | ||
| CADD | 4.637 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,820 alleles
Overall
6.21e-05%
1/1,611,132 alleles · very rare
exomes 0/1,459,052 · genomes 1/152,080 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SOS1
- Protein
- p.Val697=
- Coding
- c.2091A>T
- MANE Select
- NM_005633
- dbSNP
- rs1669533747
- Type
- single nucleotide variant
- Location
- chr2:39013536 (GRCh38)
- Gene constraint
- LOEUF 0.288 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.12 · 92 PDB
- Residue 697
- an α-helix; the n-terminal ras-gef domain
Similar variants
- SOS1 p.Val697Leu Uncertain significance ★★ ⚠ same residue
- SOS1 p.Val697Ile Uncertain significance ★★ ⚠ same residue
- SOS1 p.Arg552Gly Pathogenic ★★★ ⚠ same condition
- SOS1 p.Arg552Lys Pathogenic ★★★ ⚠ same condition
- SOS1 p.Arg552Met Likely pathogenic ★★★ ⚠ same condition
- SOS1 p.Arg552Ser Pathogenic ★★★ ⚠ same condition
- SOS1 p.Arg552Thr Pathogenic ★★★ ⚠ same condition
- SOS1 p.Arg552Trp Likely pathogenic ★★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sos1-p-val697 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown