Is WT1 p.Ser232= (c.696C>T) pathogenic?

WT1 p.Ser232= (c.696C>T) is classified Conflicting classifications of pathogenicity in WT1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-03). Rare (popmax 0.172%, eas); Associated with Inborn genetic diseases.

What condition is associated with WT1 p.Ser232= (c.696C>T)?

WT1 p.Ser232= (c.696C>T) is associated with Inborn genetic diseases, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Ser232= (c.696C>T) in the general population?

WT1 p.Ser232= (c.696C>T) is rare (popmax 0.172%, eas) (gnomAD).

WT1 p.Ser232=

c.696C>T · rs9332974 · VCV261714

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 1.3, phastCons 1
Overall
CADD	14.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% East Asian · 77/44,864 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00514% 83/1,613,976 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.172%	583
Remaining individualsnot grpmax-eligible	0.0096%	10,417

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.Ser232=
Coding: c.696C>T
MANE Select: NM_024426
dbSNP: rs9332974
Type: single nucleotide variant
Location: chr11:32428585 (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

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.Ser232Cys Uncertain significance ★ same residue
WT1 p.Ser232Gly Uncertain significance ★ same residue
WT1 p.Ser232Thr Conflicting classifications of pathogenicity ★ 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-ser232 (accessed [today's date]).

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