Is SOS2 p.Phe1031= (c.3093T>C) pathogenic?

SOS2 p.Phe1031= (c.3093T>C) is classified Likely benign in SOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with SOS2 p.Phe1031= (c.3093T>C)?

SOS2 p.Phe1031= (c.3093T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is SOS2 p.Phe1031= (c.3093T>C) in the general population?

SOS2 p.Phe1031= (c.3093T>C) is absent from gnomAD v4.1 (gnomAD).

SOS2 p.Phe1031=

c.3093T>C · VCV3447374

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 3.5	GERP 0.031, phastCons 1
Overall
CADD	9.354	PHRED · no single calibrated threshold — expert panels disagree

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.Phe1031=
Coding: c.3093T>C
MANE Select: NM_006939
Type: single nucleotide variant
Location: chr14:50130745 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.67 · 11 PDB
Residue 1031: the 'disordered' region

Full SOS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

SOS2 p.Phe1031Tyr Uncertain significance ★ ⚠ same residue
SOS2 p.Phe1031Ser Likely benign ★ same residue
SOS2 c.346-3C>T Uncertain significance ★★ same condition
SOS2 p.Ala1119Val Uncertain significance ★★ ⚠ same condition
SOS2 p.Ala62Val Uncertain significance ★★ ⚠ same condition
SOS2 p.Ala743Gly Uncertain significance ★★ ⚠ same condition
SOS2 p.Ala890Thr Uncertain significance ★★ ⚠ same condition
SOS2 p.Arg1222Leu Uncertain significance ★★ 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-phe1031 (accessed [today's date]).

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