Is SOS2 p.Pro338= (c.1014A>G) pathogenic?

SOS2 p.Pro338= (c.1014A>G) is classified Likely benign in SOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-23). Very rare (popmax 8.49e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with SOS2 p.Pro338= (c.1014A>G)?

SOS2 p.Pro338= (c.1014A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is SOS2 p.Pro338= (c.1014A>G) in the general population?

SOS2 p.Pro338= (c.1014A>G) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

SOS2 p.Pro338=

c.1014A>G · VCV4864947

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

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 -0.29	GERP -5.5, phastCons 0.43
Overall
CADD	8.812	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,988 alleles

Overall 6.21e-05% 1/1,611,010 alleles · very rare exomes 1/1,458,712 · genomes 0/152,298 · 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: SOS2
Protein: p.Pro338=
Coding: c.1014A>G
MANE Select: NM_006939
Type: single nucleotide variant
Location: chr14:50174508 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.67 · 11 PDB
Residue 338: the dh domain

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 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
SOS2 p.Arg1273Gly Uncertain significance ★★ ⚠ same condition
SOS2 p.Arg215Trp 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-pro338 (accessed [today's date]).

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