Is WT1 p.Ser328Phe (c.983C>T) pathogenic?

WT1 p.Ser328Phe (c.983C>T) is classified Uncertain significance in WT1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-22). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with WT1 p.Ser328Phe (c.983C>T)?

WT1 p.Ser328Phe (c.983C>T) is associated with Inborn genetic diseases, disorder of sexual differentiation (ClinVar).

How common is WT1 p.Ser328Phe (c.983C>T) in the general population?

WT1 p.Ser328Phe (c.983C>T) is absent from gnomAD v4.1 (gnomAD).

WT1 p.Ser328Phe

c.983C>T · rs2133032596 · VCV1202590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.159	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: WT1
Protein: p.Ser328Phe
Coding: c.983C>T
MANE Select: NM_024426
dbSNP: rs2133032596
Type: single nucleotide variant
Location: chr11:32416523 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 328: a turn

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: disorder of sexual differentiation

Similar variants

WT1 p.Ser328= Uncertain significance ★ same residue
WT1 p.Ser328Ala Likely benign ★ same residue
WT1 c.1016+4A>C Uncertain significance ★★ same condition
WT1 c.1113+5G>A Uncertain significance ★★ same condition
WT1 c.1113+5G>C Uncertain significance ★★ same condition
WT1 c.1448-3C>T Uncertain significance ★★ same condition
WT1 c.888-1G>A Uncertain significance ★★ same condition
WT1 c.965+5G>A Uncertain significance ★★ 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-ser328phe (accessed [today's date]).

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