WT1 p.Ala83Pro
c.247G>C · rs886048231 · VCV476697
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00144%, afr)
Conditions
4
Wilms tumor 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.545 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.4 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic |
| Overall | ||
| CADD | 24.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00144%
African / African-American · 1/69,488 alleles
Filtering AF
0.000519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000379%
Overall
0.000795%
12/1,510,070 alleles · very rare
exomes 12/1,358,096 · genomes 0/151,974 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00144% | 69,488 |
| European (non-Finnish) | 0.000967% | 103,384 |
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.Ala83Pro
- Coding
- c.247G>C
- MANE Select
- NM_024426
- dbSNP
- rs886048231
- Type
- single nucleotide variant
- Location
- chr11:32435114 (GRCh38)
- Gene constraint
- LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 52.09 · 31 PDB
- Residue 83
- the 'disordered' region
Similar variants
- WT1 p.Ala83Val Uncertain significance ★★ same residue
- WT1 p.Ala83Thr 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-ala83pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown