SOS2 p.Pro1177=
c.3531G>A · rs1248324702 · VCV1607778
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00267%, sas)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.9 | GERP -3.5 |
| Overall | ||
| CADD | 6.984 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
South Asian · 2/74,966 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000402%
6/1,493,424 alleles · very rare
exomes 6/1,348,962 · genomes 0/144,462 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00267% | 37,483 |
| East Asian | 0.00241% | 41,440 |
| Remaining individualsnot grpmax-eligible | 0.00176% | 56,768 |
| African / African-American | 0.00145% | 68,958 |
| European (non-Finnish) | 8.98e-05% | 1,114,160 |
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
- SOS2
- Protein
- p.Pro1177=
- Coding
- c.3531G>A
- MANE Select
- NM_006939
- dbSNP
- rs1248324702
- Type
- single nucleotide variant
- Location
- chr14:50118812 (GRCh38)
- Gene constraint
- LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.67 · 11 PDB
- Residue 1177
- the 'disordered' region
Similar variants
- SOS2 p.Pro1177Leu Uncertain significance ★★ ⚠ same residue
- SOS2 p.Met267Lys Likely pathogenic ★★★ ⚠ same condition
- SOS2 p.Ala1195Val Uncertain significance ★★★ ⚠ same condition
- SOS2 p.Arg225Gln Uncertain significance ★★★ ⚠ same condition
- SOS2 p.Arg986Lys Uncertain significance ★★★ ⚠ same condition
- SOS2 p.Thr1079Ala Uncertain significance ★★★ ⚠ same condition
- SOS2 p.Asn867Ser Likely benign ★★★ same condition
- SOS2 p.Met267Arg Pathogenic/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/sos2-p-pro1177 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown