Is WAS p.Ala433fs (c.1295dup) pathogenic?

WAS p.Ala433fs (c.1295dup) is classified Likely pathogenic in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-10). No gnomAD frequency available for this variant; Associated with Abnormality of blood and blood-forming tissues.

What condition is associated with WAS p.Ala433fs (c.1295dup)?

WAS p.Ala433fs (c.1295dup) is associated with Abnormality of blood and blood-forming tissues (ClinVar).

How common is WAS p.Ala433fs (c.1295dup) in the general population?

WAS p.Ala433fs (c.1295dup) is no gnomAD frequency available for this variant (gnomAD).

WAS p.Ala433fs

c.1295dup · rs2147266958 · VCV1180707

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Abnormality of blood and blood-forming tissues

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 1.5, phastCons 0.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: WAS
Protein: p.Ala433fs
Coding: c.1295dup
MANE Select: NM_000377
dbSNP: rs2147266958
Type: Duplication
Location: chrX:48689019 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 433: an α-helix; the wh2 domain; the 'disordered' region

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

Disease context

Abnormality of blood and blood-forming tissues — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WAS p.Ala433= Benign/Likely benign ★★ same residue
WAS p.Ala433Val Uncertain significance ★ ⚠ same residue
WAS p.Arg13fs Pathogenic ★★ same type
WAS p.Pro402_Pro404dup Uncertain significance ★★ same type
WAS c.273+10_273+11dup Benign/Likely benign ★★ same type
WAS c.273+11dup Benign/Likely benign ★★ same type
WAS c.273+9_273+11dup Likely benign ★★ same type
WAS c.560-5dup Benign/Likely benign ★★ same type

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-ala433fs (accessed [today's date]).

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