Is WAS p.Ala426Ser (c.1276G>T) pathogenic?

WAS p.Ala426Ser (c.1276G>T) is classified Benign/Likely benign in WAS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.0713); Rare (popmax 0.566%, afr); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Ala426Ser (c.1276G>T)?

WAS p.Ala426Ser (c.1276G>T) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Ala426Ser (c.1276G>T) in the general population?

WAS p.Ala426Ser (c.1276G>T) is rare (popmax 0.566%, afr) (gnomAD).

How is X-linked severe congenital neutropenia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about WAS p.Ala426Ser (c.1276G>T)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

WAS p.Ala426Ser

c.1276G>T · rs201085962 · VCV695873

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.566%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -6.86	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 1.1	GERP -0.57, phastCons 0.4
Regional constraint	o/e 0.90	unconstrained · MANE · 2,456 bp · p 0.22 · regional, not allelic
Overall
CADD	13.4	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 0.566% African / African-American · 323/57,034 alleles

Filtering AF 0.515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.496%

Overall 0.0285% 342/1,200,701 alleles · rare exomes 178/1,089,045 · genomes 164/111,656 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.566%	177
Middle Eastern	0.0235%	4,251
Remaining individualsnot grpmax-eligible	0.019%	5,257
Admixed American	0.0133%	7,504
South Asian	0.0018%	55,459
European (non-Finnish)	0.000224%	445,762

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.Ala426Ser
Coding: c.1276G>T
MANE Select: NM_000377
dbSNP: rs201085962
Type: single nucleotide variant
Location: chrX:48689004 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 426: the 'disordered' region

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

Disease context

X-linked severe congenital neutropenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Wiskott-Aldrich syndrome thrombocytopenia 1

For X-linked severe congenital neutropenia (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

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
WAS p.Ala56Val 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-ala426ser (accessed [today's date]).

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