Is WASF1 p.Pro475fs (c.1422del) pathogenic?

WASF1 p.Pro475fs (c.1422del) is classified Likely pathogenic in WASF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-27). Associated with neurodevelopmental disorder with absent language and variable seizures.

What condition is associated with WASF1 p.Pro475fs (c.1422del)?

WASF1 p.Pro475fs (c.1422del) is associated with neurodevelopmental disorder with absent language and variable seizures (ClinVar).

WASF1 p.Pro475fs

c.1422del · VCV4796709

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder with absent language and variable seizures

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.7	GERP 3.5, phastCons 1

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

Variant & gene context

Gene: WASF1
Protein: p.Pro475fs
Coding: c.1422del
MANE Select: NM_003931
Type: Deletion
Location: chr6:110101688 (GRCh38)
Gene constraint: LOEUF 0.301 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.26 · 5 PDB
Residue 475: the 'disordered' region

Full WASF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with absent language and variable seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WASF1 p.Pro492fs Pathogenic ★ same condition
WASF1 p.Glu175_Lys178del Uncertain significance ★ same condition
WASF1 p.Arg506Ter Pathogenic ★★ same condition
WASF1 c.270_271del Likely pathogenic ★ same condition
WASF1 p.Glu88Ter Pathogenic ★ same condition
WASF1 p.Met165fs Pathogenic ★ same condition
WASF1 p.Ser489Ter Likely pathogenic ★ same condition
WASF1 p.Ala218Thr Uncertain significance ★ ⚠ 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/wasf1-p-pro475fs (accessed [today's date]).

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