SOS1 p.Asp190=
c.570C>T · rs55980502 · VCV40655
ClinGen expert panel — RASopathy VCEP
Benign for RASopathy. Applied ACMG criteria (verbatim):
BA1
Curation rationale (ClinGen, verbatim)
The filtering allele frequency of the c.570C>T (p.Asp190=) variant in the SOS1 gene is 0.314% (234/66628) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 7 | GERP 0.49, phastCons 1 |
| Overall | ||
| CADD | 13.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.691% | 145 |
| European (non-Finnish)grpmax | 0.246% | 406 |
| Remaining individualsnot grpmax-eligible | 0.236% | 424 |
| Middle Eastern | 0.2% | 500 |
| Admixed American | 0.135% | 740 |
| African / African-American | 0.0551% | 1,814 |
| South Asian | 0.0453% | 2,205 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0272% | 3,675 |
| East Asian | 0.0269% | 3,719 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Asp190=
- Coding
- c.570C>T
- MANE Select
- NM_005633
- dbSNP
- rs55980502
- Type
- single nucleotide variant
- Location
- chr2:39054764 (GRCh38)
- Gene constraint
- LOEUF 0.288 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.12 · 92 PDB
Similar variants
- SOS1 p.Asp190His Uncertain significance ★ ⚠ same residue
- SOS1 p.Asp190Glu 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-asp190 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown