SOS1 p.Pro112=
c.336T>A · rs1345058035 · VCV1730722
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Conditions
1
Cardiovascular phenotype
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 4.7 | GERP -0.76, phastCons 1 |
| Overall | ||
| CADD | 11.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,186 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,612,910 alleles · very rare
exomes 2/1,460,740 · genomes 0/152,170 · 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.Pro112=
- Coding
- c.336T>A
- MANE Select
- NM_005633
- dbSNP
- rs1345058035
- Type
- single nucleotide variant
- Location
- chr2:39058682 (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 112
- a UniProt-annotated variant site (in ns4); an α-helix
Similar variants
- SOS1 p.Pro112Ala Uncertain significance ★ ⚠ same residue
- SOS1 p.Pro112Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- SOS1 p.Pro112Leu Uncertain significance ★ same residue
- SOS1 p.Gly434Arg Pathogenic ★★ same condition
- SOS1 p.Ile437Thr Pathogenic/Likely pathogenic ★★ same condition
- SOS1 p.Leu550Pro Pathogenic/Likely pathogenic ★★ same condition
- SOS1 c.720+1G>A Uncertain significance ★★ same condition
- SOS1 p.Ala1162Val Uncertain significance ★★ ⚠ 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-pro112 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown