Is WASF2 p.Pro350Arg (c.1049C>G) pathogenic?

WASF2 p.Pro350Arg (c.1049C>G) is classified Uncertain significance in WASF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.2705); Absent from gnomAD v4.1.

How common is WASF2 p.Pro350Arg (c.1049C>G) in the general population?

WASF2 p.Pro350Arg (c.1049C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WASF2 p.Pro350Arg (c.1049C>G)?

AlphaMissense predicts likely benign (score 0.2705) — an in-silico prediction, not a clinical call.

WASF2 p.Pro350Arg

c.1049C>G · VCV4200102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2705 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2705	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -12.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 6,664 bp · p 6e-06 · regional, not allelic
Overall
CADD	23.3	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: WASF2
Protein: p.Pro350Arg
Coding: c.1049C>G
MANE Select: NM_006990
Type: single nucleotide variant
Location: chr1:27409982 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB
Residue 350: the 'disordered' region

Full WASF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WASF2 p.Pro247Leu Likely benign ★★ same type
WASF2 p.Ala317Val Uncertain significance ★ ⚠ same type
WASF2 p.Ala372Ser Uncertain significance ★ ⚠ same type
WASF2 p.Arg451Cys Uncertain significance ★ ⚠ same type
WASF2 p.Arg64Trp Uncertain significance ★ ⚠ same type
WASF2 p.Arg74Gln Uncertain significance ★ ⚠ same type
WASF2 p.Asn135Ser Uncertain significance ★ ⚠ same type
WASF2 p.Asn59Asp Uncertain significance ★ ⚠ 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/wasf2-p-pro350arg (accessed [today's date]).

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