Is WT1 p.Val376fs (c.1125dup) pathogenic?

WT1 p.Val376fs (c.1125dup) is classified Pathogenic in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-05). Associated with Wilms tumor 1.

What condition is associated with WT1 p.Val376fs (c.1125dup)?

WT1 p.Val376fs (c.1125dup) is associated with Wilms tumor 1 (ClinVar).

WT1 p.Val376fs

c.1125dup · VCV4857435

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Wilms tumor 1

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 7 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 2.7, phastCons 1

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

Variant & gene context

Gene: WT1
Protein: p.Val376fs
Coding: c.1125dup
MANE Select: NM_024426
Type: Duplication
Location: chr11:32396395 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 376: the 'important for interaction with target dna' region; an α-helix

Full WT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wilms tumor 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WT1 p.Val376Ala Uncertain significance ★★ same residue
WT1 p.Val376Met Uncertain significance ★ same residue
WT1 p.Thr279fs Pathogenic ★★ same condition
WT1 p.Pro136_Pro141dup Uncertain significance ★★ same condition
WT1 p.Asn246fs Pathogenic ★ same condition
WT1 p.Asp228fs Pathogenic ★ same condition
WT1 p.His416fs Likely pathogenic ★ same condition
WT1 p.Phe396fs 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/wt1-p-val376fs (accessed [today's date]).

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