Is SOS1 p.Asp366Val (c.1097A>T) pathogenic?

SOS1 p.Asp366Val (c.1097A>T) is classified Likely benign in SOS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely benign (0.2592); Very rare (popmax 0.00668%, afr); Associated with RASopathy.

What condition is associated with SOS1 p.Asp366Val (c.1097A>T)?

SOS1 p.Asp366Val (c.1097A>T) is associated with RASopathy (ClinVar).

How common is SOS1 p.Asp366Val (c.1097A>T) in the general population?

SOS1 p.Asp366Val (c.1097A>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about SOS1 p.Asp366Val (c.1097A>T)?

AlphaMissense predicts likely benign (score 0.2592) — an in-silico prediction, not a clinical call.

SOS1 p.Asp366Val

c.1097A>T · rs1056080833 · VCV566072

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.2592	likely benign
REVEL	0.676	pathogenic-leaning
SaProt	LLR -10.47	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 28 kb · p 7.4e-08 · regional, not allelic
Overall
CADD	25.8	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

Grpmax group 0.00668% African / African-American · 5/74,880 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00031% 5/1,611,232 alleles · very rare exomes 2/1,459,038 · genomes 3/152,194 · 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.Asp366Val
Coding: c.1097A>T
MANE Select: NM_005633
dbSNP: rs1056080833
Type: single nucleotide variant
Location: chr2:39024115 (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 366: the dh domain

Full SOS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOS1 p.Asp366Tyr Uncertain significance ★★ ⚠ same residue
SOS1 p.Asp366Glu Conflicting classifications of pathogenicity ★ ⚠ 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-asp366val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown