Is WAS p.Gln33Glu (c.97C>G) pathogenic?

WAS p.Gln33Glu (c.97C>G) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely benign (0.0856); Very rare (popmax 0.000447%, nfe); Associated with Wiskott-Aldrich syndrome.

What condition is associated with WAS p.Gln33Glu (c.97C>G)?

WAS p.Gln33Glu (c.97C>G) is associated with Wiskott-Aldrich syndrome, X-linked severe congenital neutropenia, thrombocytopenia 1 (ClinVar).

How common is WAS p.Gln33Glu (c.97C>G) in the general population?

WAS p.Gln33Glu (c.97C>G) is very rare (popmax 0.000447%, nfe) (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.Gln33Glu (c.97C>G)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

WAS p.Gln33Glu

c.97C>G · rs1569493682 · VCV566906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Wiskott-Aldrich syndrome

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.453	indeterminate
SaProt	LLR -4.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 1,973 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	18.42	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 0.000447% European (non-Finnish) · 4/895,406 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.00033% 4/1,211,406 alleles · very rare exomes 4/1,098,248 · genomes 0/113,158 · 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.Gln33Glu
Coding: c.97C>G
MANE Select: NM_000377
dbSNP: rs1569493682
Type: single nucleotide variant
Location: chrX:48683950 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB

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-gln33glu (accessed [today's date]).

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