SOS2 p.Thr830=
c.2490C>T · rs1269639034 · VCV1792061
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000341%, nfe)
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 -3.4 | GERP -3.7 |
| Overall | ||
| CADD | 0.831 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000341%
European (non-Finnish) · 4/1,173,044 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.00025%
4/1,603,088 alleles · very rare
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.Thr830=
- Coding
- c.2490C>T
- MANE Select
- NM_006939
- dbSNP
- rs1269639034
- Type
- single nucleotide variant
- Location
- chr14:50145491 (GRCh38)
- Gene constraint
- LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.67 · 11 PDB
- Residue 830
- the ras-gef domain; an α-helix
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-thr830 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown