Is WT1 p.Pro137fs (c.410del) pathogenic?

WT1 p.Pro137fs (c.410del) is classified Pathogenic/Likely pathogenic in WT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-04). Very rare (popmax 6.52e-05%); Associated with Denys-Drash syndrome.

What condition is associated with WT1 p.Pro137fs (c.410del)?

WT1 p.Pro137fs (c.410del) is associated with Denys-Drash syndrome, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Pro137fs (c.410del) in the general population?

WT1 p.Pro137fs (c.410del) is very rare (popmax 6.52e-05%) (gnomAD).

How is Denys-Drash syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

WT1 p.Pro137fs

c.410del · rs2494480771 · VCV2664749

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.52e-05%)

Conditions

Denys-Drash syndrome

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 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1	GERP 0.084, phastCons 0.004
Region caveats
Repeat context	tandem	(GGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.52e-05%

Overall 6.52e-05% 1/1,532,618 alleles · very rare exomes 1/1,381,672 · genomes 0/150,946 · 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: WT1
Protein: p.Pro137fs
Coding: c.410del
MANE Select: NM_024426
dbSNP: rs2494480771
Type: Deletion
Location: chr11:32434951 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB

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

Disease context

Denys-Drash syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Frasier syndrome Wilms tumor 1 WAGR syndrome

For Denys-Drash syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

WT1 p.Pro137_Pro141del Uncertain significance ★ same residue
WT1 p.Pro137Ala Uncertain significance ★★ same residue
WT1 p.Pro137= Likely benign ★ same residue
WT1 c.1354+4_1354+11del Likely pathogenic ★ same condition
WT1 c.882_887+3del Pathogenic ★ same condition
WT1 p.Arg476fs Likely pathogenic ★ same condition
WT1 p.Arg500fs Likely pathogenic ★ same condition
WT1 p.Gln457_Cys458insTer 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-pro137fs (accessed [today's date]).

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