SOS1 p.Arg552=
c.1656G>A · VCV3447329
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, 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 0.6 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 7.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,179,648 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,613,648 alleles · very rare
exomes 6/1,461,482 · genomes 0/152,166 · 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.Arg552=
- Coding
- c.1656G>A
- MANE Select
- NM_005633
- Type
- single nucleotide variant
- Location
- chr2:39022772 (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 552
- a UniProt-annotated variant site (in ns4; increases the basal level of active ras; prolonges ras activation after egf stimulation and enhances erk activation); a UniProt-annotated variant site (in ns4)
Similar variants
- SOS1 p.Arg552Gly Pathogenic ★★★ ⚠ same residue
- SOS1 p.Arg552Lys Pathogenic ★★★ ⚠ same residue
- SOS1 p.Arg552Met Likely pathogenic ★★★ ⚠ same residue
- SOS1 p.Arg552Ser Pathogenic ★★★ ⚠ same residue
- SOS1 p.Arg552Thr Pathogenic ★★★ ⚠ same residue
- SOS1 p.Arg552Trp Likely pathogenic ★★★ same residue
- SOS1 p.Gly434Arg Pathogenic ★★ same condition
- SOS1 p.Ile437Thr 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/sos1-p-arg552 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown