Is WT1 p.Pro269= (c.807G>T) pathogenic?

WT1 p.Pro269= (c.807G>T) is classified Likely benign in WT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-30). Very rare (popmax 0.000595%, nfe); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Pro269= (c.807G>T)?

WT1 p.Pro269= (c.807G>T) is associated with Wilms tumor 1 (ClinVar).

How common is WT1 p.Pro269= (c.807G>T) in the general population?

WT1 p.Pro269= (c.807G>T) is very rare (popmax 0.000595%, nfe) (gnomAD).

WT1 p.Pro269=

c.807G>T · VCV3982432

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000595%, nfe)

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -4.2
Overall
CADD	9.504	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000595% European (non-Finnish) · 7/1,177,074 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000435% 7/1,608,696 alleles · very rare exomes 7/1,456,386 · genomes 0/152,310 · 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.Pro269=
Coding: c.807G>T
MANE Select: NM_024426
Type: single nucleotide variant
Location: chr11:32428036 (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

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

Similar variants

WT1 p.Pro269Leu Uncertain significance ★★ same residue
WT1 p.Pro269Arg Conflicting classifications of pathogenicity ★ same residue
WT1 p.Pro269Gln Uncertain significance ★ same residue
WT1 c.1354+2T>C Pathogenic/Likely pathogenic ★★ same condition
WT1 c.1447+2T>C Pathogenic ★★ same condition
WT1 c.1447+4C>T Pathogenic/Likely pathogenic ★★ same condition
WT1 c.1447+5G>A Pathogenic/Likely pathogenic ★★ same condition
WT1 c.1448-1G>A Pathogenic/Likely 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-pro269 (accessed [today's date]).

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