Is WT1 p.Ser466Phe (c.1397C>T) pathogenic?

WT1 p.Ser466Phe (c.1397C>T) is classified Pathogenic in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-23). Very rare (popmax 0.00351%, amr); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Ser466Phe (c.1397C>T)?

WT1 p.Ser466Phe (c.1397C>T) is associated with Wilms tumor 1, malignant mesothelioma, Frasier syndrome (ClinVar).

How common is WT1 p.Ser466Phe (c.1397C>T) in the general population?

WT1 p.Ser466Phe (c.1397C>T) is very rare (popmax 0.00351%, amr) (gnomAD).

WT1 p.Ser466Phe

c.1397C>T · VCV3599545

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00351%, amr)

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.4	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 7,138 bp · p 4.9e-17 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00351% Admixed American · 2/56,954 alleles

Filtering AF 0.000582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000126% 2/1,583,942 alleles · very rare exomes 1/1,452,318 · genomes 1/131,624 · 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.Ser466Phe
Coding: c.1397C>T
MANE Select: NM_024426
Type: single nucleotide variant
Location: chr11:32392022 (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: malignant mesothelioma Frasier syndrome Denys-Drash syndrome nephrotic syndrome, type 4 Meacham syndrome

Similar variants

WT1 p.Ser466= 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-ser466phe (accessed [today's date]).

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