Is SOS2 p.Ala314= (c.942C>G) pathogenic?

SOS2 p.Ala314= (c.942C>G) is classified Likely benign in SOS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-07). Absent from gnomAD v4.1; Associated with Noonan syndrome 9.

What condition is associated with SOS2 p.Ala314= (c.942C>G)?

SOS2 p.Ala314= (c.942C>G) is associated with Noonan syndrome 9 (ClinVar).

How common is SOS2 p.Ala314= (c.942C>G) in the general population?

SOS2 p.Ala314= (c.942C>G) is absent from gnomAD v4.1 (gnomAD).

SOS2 p.Ala314=

c.942C>G · rs2503093384 · VCV1766921

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 1.5	GERP -0.59, phastCons 1
Overall
CADD	8.644	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.Ala314=
Coding: c.942C>G
MANE Select: NM_006939
dbSNP: rs2503093384
Type: single nucleotide variant
Location: chr14:50180599 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.67 · 11 PDB
Residue 314: the dh domain

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

Disease context

Noonan syndrome 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOS2 p.Ala314Thr Uncertain significance ★ ⚠ same residue
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

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-ala314 (accessed [today's date]).

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