Is WAS p.Arg357Trp (c.1069C>T) pathogenic?

WAS p.Arg357Trp (c.1069C>T) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-23). AlphaMissense: likely benign (0.1369); Very rare (popmax 0.0027%, amr); Associated with Wiskott-Aldrich syndrome.

What condition is associated with WAS p.Arg357Trp (c.1069C>T)?

WAS p.Arg357Trp (c.1069C>T) is associated with Wiskott-Aldrich syndrome, X-linked severe congenital neutropenia, thrombocytopenia 1 (ClinVar).

How common is WAS p.Arg357Trp (c.1069C>T) in the general population?

WAS p.Arg357Trp (c.1069C>T) is very rare (popmax 0.0027%, amr) (gnomAD).

How is Wiskott-Aldrich syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about WAS p.Arg357Trp (c.1069C>T)?

AlphaMissense predicts likely benign (score 0.1369) — an in-silico prediction, not a clinical call.

WAS p.Arg357Trp

c.1069C>T · VCV4793099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Wiskott-Aldrich syndrome

Computational evidence

Protein change
AlphaMissense	0.1369	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -10.90	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP 0.28, phastCons 0.03
Regional constraint	o/e 0.90	unconstrained · MANE · 2,456 bp · p 0.22 · regional, not allelic
Overall
CADD	22.6	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

Grpmax group 0.0027% Admixed American · 1/37,030 alleles

Overall 0.000179% 2/1,119,519 alleles · very rare exomes 2/1,006,985 · genomes 0/112,534 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0027%	37,030
European (non-Finnish)	0.000119%	839,891

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.Arg357Trp
Coding: c.1069C>T
MANE Select: NM_000377
Type: single nucleotide variant
Location: chrX:48688797 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 357: the 'disordered' region

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

Disease context

Wiskott-Aldrich syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked severe congenital neutropenia thrombocytopenia 1

For Wiskott-Aldrich syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

WAS p.Arg357Gln Uncertain significance ★★ ⚠ 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-arg357trp (accessed [today's date]).

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