Is WT1 p.Cys161= (c.483C>T) pathogenic?

WT1 p.Cys161= (c.483C>T) is classified Likely benign in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). Very rare (popmax 8.48e-05%, nfe); Associated with WAGR syndrome.

What condition is associated with WT1 p.Cys161= (c.483C>T)?

WT1 p.Cys161= (c.483C>T) is associated with WAGR syndrome, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Cys161= (c.483C>T) in the general population?

WT1 p.Cys161= (c.483C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

WT1 p.Cys161=

c.483C>T · rs773922379 · VCV2146748

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

WAGR syndrome

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 0.17	GERP -1.4, phastCons 0.001
Overall
CADD	10.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,830 alleles

Overall 6.2e-05% 1/1,612,470 alleles · very rare exomes 1/1,460,124 · genomes 0/152,346 · 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.Cys161=
Coding: c.483C>T
MANE Select: NM_024426
dbSNP: rs773922379
Type: single nucleotide variant
Location: chr11:32434878 (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

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

Also linked: Frasier syndrome Wilms tumor 1 Denys-Drash syndrome

Similar variants

WT1 p.Cys161Phe Uncertain significance ★★ same residue
WT1 p.Cys161Gly Uncertain significance ★ 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

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-cys161 (accessed [today's date]).

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