Is WAS p.Arg321Gln (c.962G>A) pathogenic?

WAS p.Arg321Gln (c.962G>A) is classified Uncertain significance in WAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.1339); Very rare (popmax 0.00135%, nfe); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Arg321Gln (c.962G>A)?

WAS p.Arg321Gln (c.962G>A) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Arg321Gln (c.962G>A) in the general population?

WAS p.Arg321Gln (c.962G>A) is very rare (popmax 0.00135%, nfe) (gnomAD).

What do computational predictors say about WAS p.Arg321Gln (c.962G>A)?

AlphaMissense predicts likely benign (score 0.1339) — an in-silico prediction, not a clinical call.

WAS p.Arg321Gln

c.962G>A · rs782802310 · VCV1047669

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

thrombocytopenia 1

Computational evidence

Protein change
AlphaMissense	0.1339	likely benign
REVEL	0.419	indeterminate
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 2,597 bp · p 6e-07 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% European (non-Finnish) · 12/887,635 alleles

Filtering AF 0.000721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000569%

Overall 0.001% 12/1,195,044 alleles · very rare exomes 11/1,085,893 · genomes 1/109,151 · 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: WAS
Protein: p.Arg321Gln
Coding: c.962G>A
MANE Select: NM_000377
dbSNP: rs782802310
Type: single nucleotide variant
Location: chrX:48688690 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 321: the 'disordered' region

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

Disease context

thrombocytopenia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked severe congenital neutropenia Wiskott-Aldrich syndrome

Similar variants

WAS p.Arg321Ter Pathogenic ★★ same residue
WAS c.1339-2A>G Pathogenic/Likely pathogenic ★★ same condition
WAS c.1453+2T>C Pathogenic ★★ same condition
WAS c.273+1G>A Pathogenic ★★ same condition
WAS c.360+1G>A Pathogenic ★★ same condition
WAS c.559+5G>A Pathogenic ★★ same condition
WAS c.777+1G>A Pathogenic ★★ same condition
WAS c.778-6G>A 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/was-p-arg321gln (accessed [today's date]).

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