Is WT1 p.Pro377= (c.1131T>C) pathogenic?

WT1 p.Pro377= (c.1131T>C) is classified Conflicting classifications of pathogenicity in WT1 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-02-04). Ultra-rare (popmax 0.0867%, nfe); Associated with Inborn genetic diseases.

What condition is associated with WT1 p.Pro377= (c.1131T>C)?

WT1 p.Pro377= (c.1131T>C) is associated with Inborn genetic diseases, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Pro377= (c.1131T>C) in the general population?

WT1 p.Pro377= (c.1131T>C) is ultra-rare (popmax 0.0867%, nfe) (gnomAD).

WT1 p.Pro377=

c.1131T>C · rs151034312 · VCV198590

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0867%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.09	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -5.4
Overall
CADD	0.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0867% European (non-Finnish) · 1,023/1,180,050 alleles

Filtering AF 0.0822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0805%

Overall 0.0683% 1,103/1,614,116 alleles · ultra-rare exomes 1,032/1,461,790 · genomes 71/152,326 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0867%	1,154
Admixed American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.0512%	1,953
African / African-American	0.0147%	6,823
Finnishnot grpmax-eligible	0.00781%	12,798

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.Pro377=
Coding: c.1131T>C
MANE Select: NM_024426
dbSNP: rs151034312
Type: single nucleotide variant
Location: chr11:32396390 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 377: a UniProt-annotated variant site (in dds); a UniProt-annotated variant site (in nphs4); 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Frasier syndrome Wilms tumor 1 WAGR syndrome Denys-Drash syndrome nephrotic syndrome, type 4 Meacham syndrome hereditary neoplastic syndrome

Similar variants

WT1 p.Pro377His Uncertain significance ★ same residue
WT1 p.Pro377Ser 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
WT1 p.Arg374Ter 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-pro377 (accessed [today's date]).

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