SOS2 p.Asp161=
c.483C>T · rs1012615333 · VCV2884314
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00675%, amr)
Conditions
1
Noonan syndrome 9
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 1.3 | GERP 0.23, phastCons 1 |
| Overall | ||
| CADD | 8.772 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00675%
Admixed American · 4/59,240 alleles
Filtering AF
0.00228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000311%
5/1,608,146 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00675% | 14,810 |
| European (non-Finnish) | 8.5e-05% | 1,176,566 |
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.Asp161=
- Coding
- c.483C>T
- MANE Select
- NM_006939
- dbSNP
- rs1012615333
- Type
- single nucleotide variant
- Location
- chr14:50199718 (GRCh38)
- Gene constraint
- LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.67 · 11 PDB
Similar variants
- 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
- SOS2 p.Met267Thr 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-asp161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown