Is WT1 p.Ser346= (c.1038C>T) pathogenic?

WT1 p.Ser346= (c.1038C>T) is classified Likely benign in WT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-03). Very rare (popmax 0.00801%, afr); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Ser346= (c.1038C>T)?

WT1 p.Ser346= (c.1038C>T) is associated with Wilms tumor 1, malignant mesothelioma, Frasier syndrome (ClinVar).

How common is WT1 p.Ser346= (c.1038C>T) in the general population?

WT1 p.Ser346= (c.1038C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

WT1 p.Ser346=

c.1038C>T · rs750018485 · VCV543156

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.1	GERP -5.1
Overall
CADD	0.386	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,932 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000434% 7/1,614,096 alleles · very rare exomes 3/1,461,884 · genomes 4/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,489
European (non-Finnish)	8.47e-05%	1,180,052

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.Ser346=
Coding: c.1038C>T
MANE Select: NM_024426
dbSNP: rs750018485
Type: single nucleotide variant
Location: chr11:32400023 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 346: an α-helix

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 WAGR syndrome Denys-Drash syndrome nephrotic syndrome, type 4 Meacham syndrome aniridia 1

Similar variants

WT1 p.Ser346Arg Uncertain significance ★★ same residue
WT1 p.Ser346Asn Uncertain significance ★ same residue
WT1 p.Ser346Cys Uncertain significance ★ same residue
WT1 p.Ser346Gly Pathogenic 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

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-ser346 (accessed [today's date]).

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