Is WT1 p.Pro352Ala (c.1054C>G) pathogenic?

WT1 p.Pro352Ala (c.1054C>G) is classified Uncertain significance in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-18). Ultra-rare (popmax 0.0165%, mid); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Pro352Ala (c.1054C>G)?

WT1 p.Pro352Ala (c.1054C>G) is associated with Wilms tumor 1, Frasier syndrome, WAGR syndrome (ClinVar).

How common is WT1 p.Pro352Ala (c.1054C>G) in the general population?

WT1 p.Pro352Ala (c.1054C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

WT1 p.Pro352Ala

c.1054C>G · rs2132958327 · VCV2923864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.535	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.19e-05% 1/1,614,220 alleles · ultra-rare exomes 1/1,461,890 · genomes 0/152,330 · 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.Pro352Ala
Coding: c.1054C>G
MANE Select: NM_024426
dbSNP: rs2132958327
Type: single nucleotide variant
Location: chr11:32400007 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 352: a β-strand

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.Pro352= Likely benign ★★ 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
WT1 p.Arg435Ter 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-pro352ala (accessed [today's date]).

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