Is WT1 p.Ser346Cys (c.1035_1036delinsAT) pathogenic?

WT1 p.Ser346Cys (c.10351036delinsAT) is classified Uncertain significance in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-10). No gnomAD frequency available for this variant; Associated with Denys-Drash syndrome.

What condition is associated with WT1 p.Ser346Cys (c.1035_1036delinsAT)?

WT1 p.Ser346Cys (c.1035_1036delinsAT) is associated with Denys-Drash syndrome, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Ser346Cys (c.1035_1036delinsAT) in the general population?

WT1 p.Ser346Cys (c.1035_1036delinsAT) is no gnomAD frequency available for this variant (gnomAD).

How is Denys-Drash syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

WT1 p.Ser346Cys

c.1035_1036delinsAT · rs2132958801 · VCV1442038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Denys-Drash syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: WT1
Protein: p.Ser346Cys
Coding: c.1035_1036delinsAT
MANE Select: NM_024426
dbSNP: rs2132958801
Type: Indel
Location: chr11:32400025 (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

Denys-Drash syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Frasier syndrome Wilms tumor 1 WAGR syndrome

For Denys-Drash syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

WT1 p.Ser346Arg Uncertain significance ★★ same residue
WT1 p.Ser346= Likely benign ★★ same residue
WT1 p.Ser346Asn Uncertain significance ★ same residue
WT1 p.Arg385fs Pathogenic/Likely pathogenic ★★ same condition
WT1 p.Ala10Ile Uncertain significance ★★ same condition
WT1 p.Arg374Gln Uncertain significance ★★ same condition
WT1 p.Arg374Trp Uncertain significance ★★ same condition
WT1 c.887+15_887+16delinsAA 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-ser346cys (accessed [today's date]).

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