Is WAS p.Ala92Thr (c.274G>A) pathogenic?

WAS p.Ala92Thr (c.274G>A) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.00185%, sas); Associated with Wiskott-Aldrich syndrome.

What condition is associated with WAS p.Ala92Thr (c.274G>A)?

WAS p.Ala92Thr (c.274G>A) is associated with Wiskott-Aldrich syndrome, X-linked severe congenital neutropenia, thrombocytopenia 1 (ClinVar).

How common is WAS p.Ala92Thr (c.274G>A) in the general population?

WAS p.Ala92Thr (c.274G>A) is very rare (popmax 0.00185%, sas) (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.Ala92Thr (c.274G>A)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

WAS p.Ala92Thr

c.274G>A · VCV3750932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00185%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Wiskott-Aldrich syndrome

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 0.48, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 1,973 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	20.3	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 0.00185% South Asian · 1/54,128 alleles

Overall 8.39e-05% 1/1,192,570 alleles · very rare exomes 1/1,079,182 · genomes 0/113,388 · 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.Ala92Thr
Coding: c.274G>A
MANE Select: NM_000377
Type: single nucleotide variant
Location: chrX:48685547 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 92: the wh1 domain

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 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-ala92thr (accessed [today's date]).

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