Is WAS p.Ala418Val (c.1253C>T) pathogenic?

WAS p.Ala418Val (c.1253C>T) is classified Likely benign in WAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0697); Ultra-rare (popmax 0.072%, mid); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Ala418Val (c.1253C>T)?

WAS p.Ala418Val (c.1253C>T) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Ala418Val (c.1253C>T) in the general population?

WAS p.Ala418Val (c.1253C>T) is ultra-rare (popmax 0.072%, mid) (gnomAD).

What do computational predictors say about WAS p.Ala418Val (c.1253C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

WAS p.Ala418Val

c.1253C>T · rs781903491 · VCV696934

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.072%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

thrombocytopenia 1

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -0.72, phastCons 0.002
Regional constraint	o/e 0.90	unconstrained · MANE · 2,456 bp · p 0.22 · regional, not allelic
Overall
CADD	11.28	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 0.072% Middle Eastern · 3/4,166 alleles

Filtering AF 0.0196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.00596% 71/1,190,543 alleles · ultra-rare exomes 69/1,078,638 · genomes 2/111,905 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.072%	1,389
European (non-Finnish)	0.00689%	14,523
South Asian	0.00554%	18,062
Admixed American	0.00463%	21,577
African / African-American	0.00352%	28,407

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.Ala418Val
Coding: c.1253C>T
MANE Select: NM_000377
dbSNP: rs781903491
Type: single nucleotide variant
Location: chrX:48688981 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 418: 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.Ala418Thr Uncertain significance ★ ⚠ same residue
WAS p.Ala418Ser Benign ★ 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

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-ala418val (accessed [today's date]).

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