SOS2 p.Arg720Ser
c.2160A>C · VCV4529805
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.5796 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5796 | likely pathogenic |
|---|---|---|
| REVEL | 0.085 | moderately benign-leaning |
| SaProt | LLR -6.23 | tolerated |
| ⇒ AlphaMissense calls this damaging; REVEL and SaProt do not. | ||
| Splicing | ||
| SpliceAI | Δ0.76 | donor loss · deltas |
| Pangolin | Δ0.64 | loss · gain 0.48 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.81 | unconstrained · MANE · 29 kb · p 1.2e-05 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SOS2
- Protein
- p.Arg720Ser
- Coding
- c.2160A>C
- MANE Select
- NM_006939
- Type
- single nucleotide variant
- Location
- chr14:50153071 (GRCh38)
- Gene constraint
- LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.67 · 11 PDB
- Residue 720
- the n-terminal ras-gef domain
Similar variants
- SOS2 p.Met267Lys Likely pathogenic ★★★ ⚠ same type
- SOS2 p.Ala1195Val Uncertain significance ★★★ ⚠ same type
- SOS2 p.Arg225Gln Uncertain significance ★★★ ⚠ same type
- SOS2 p.Arg986Lys Uncertain significance ★★★ ⚠ same type
- SOS2 p.Thr1079Ala Uncertain significance ★★★ ⚠ same type
- SOS2 p.Asn867Ser Likely benign ★★★ same type
- SOS2 p.Met267Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
- SOS2 p.Met267Thr Pathogenic ★★ ⚠ same type
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-arg720ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown