Is WT1 p.Pro271fs (c.812del) pathogenic?

WT1 p.Pro271fs (c.812del) is classified Pathogenic in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-12). Very rare (popmax 0.00223%, eas); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Pro271fs (c.812del)?

WT1 p.Pro271fs (c.812del) is associated with Wilms tumor 1, Frasier syndrome, WAGR syndrome (ClinVar).

How common is WT1 p.Pro271fs (c.812del) in the general population?

WT1 p.Pro271fs (c.812del) is very rare (popmax 0.00223%, eas) (gnomAD).

WT1 p.Pro271fs

c.812del · rs1060501253 · VCV406680

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 3 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20	GERP -4.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,778 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000311% 5/1,609,758 alleles · very rare exomes 5/1,457,446 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,778
European (non-Finnish)	0.00034%	294,417

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.Pro271fs
Coding: c.812del
MANE Select: NM_024426
dbSNP: rs1060501253
Type: Deletion
Location: chr11:32428031 (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

Also linked: Frasier syndrome WAGR syndrome Denys-Drash syndrome

Similar variants

WT1 p.Pro271Gln Uncertain significance ★ same residue
WT1 p.Pro137fs Pathogenic/Likely pathogenic ★★ same condition
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
WT1 p.Glu423fs 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-pro271fs (accessed [today's date]).

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