Is WT1 p.Asp228= (c.684C>T) pathogenic?

WT1 p.Asp228= (c.684C>T) is classified Likely benign in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-24). No allele count reported in gnomAD v4.1 (AN 1,613,698); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Asp228= (c.684C>T)?

WT1 p.Asp228= (c.684C>T) is associated with Wilms tumor 1, Frasier syndrome, WAGR syndrome (ClinVar).

How common is WT1 p.Asp228= (c.684C>T) in the general population?

WT1 p.Asp228= (c.684C>T) is no allele count reported in gnomAD v4.1 (AN 1,613,698) (gnomAD).

WT1 p.Asp228=

c.684C>T · VCV3757829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,698)

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 -0.96	GERP -4.5
Overall
CADD	5.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,698). 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.Asp228=
Coding: c.684C>T
MANE Select: NM_024426
Type: single nucleotide variant
Location: chr11:32428597 (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: Frasier syndrome WAGR syndrome Denys-Drash syndrome

Similar variants

WT1 p.Asp228Asn Uncertain significance ★ same residue
WT1 p.Asp228Tyr Uncertain significance ★ same residue
WT1 p.Asp228fs Pathogenic ★ same residue
WT1 p.Asp228His Uncertain significance ★ same residue
WT1 p.Asp228Val 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

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-asp228 (accessed [today's date]).

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