WT1 p.Ser296Cys
c.886A>T · VCV4758803
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000594%, nfe)
Conditions
1
Wilms tumor 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.779 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.46 | donor loss, 1 bp away · masked 0 · deltas |
| Pangolin | Δ0.28 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic |
| Overall | ||
| CADD | 26.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000594%
European (non-Finnish) · 7/1,177,924 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000435%
7/1,608,988 alleles · very rare
exomes 7/1,456,746 · genomes 0/152,242 · 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.Ser296Cys
- Coding
- c.886A>T
- MANE Select
- NM_024426
- Type
- single nucleotide variant
- Location
- chr11:32427957 (GRCh38)
- Gene constraint
- LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 52.09 · 31 PDB
Similar variants
- WT1 p.Ser296Arg 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
- WT1 p.Arg435Ter 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-ser296cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown