SOS1 p.Asp910=
c.2730T>C · rs1669285499 · VCV2794621
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00224%, eas)
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 9.4 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 9.593 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00224%
East Asian · 1/44,736 alleles
Overall
6.21e-05%
1/1,610,344 alleles · very rare
exomes 1/1,458,104 · genomes 0/152,240 · 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.Asp910=
- Coding
- c.2730T>C
- MANE Select
- NM_005633
- dbSNP
- rs1669285499
- Type
- single nucleotide variant
- Location
- chr2:39006473 (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 910
- an α-helix; the ras-gef domain
Similar variants
- SOS1 p.Asp910His Uncertain significance ★★★ ⚠ same residue
- SOS1 p.Asp910Asn 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-asp910 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown