WT1 p.Gln427=
c.1281G>A · rs774650640 · VCV792544
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
5
Inborn genetic diseases
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 0.81 | GERP -0.48, phastCons 1 |
| Overall | ||
| CADD | 6.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,998 alleles
Overall
0.000124%
2/1,613,874 alleles · very rare
exomes 1/1,461,714 · genomes 1/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,998 |
| European (non-Finnish) | 8.48e-05% | 1,179,894 |
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.Gln427=
- Coding
- c.1281G>A
- MANE Select
- NM_024426
- dbSNP
- rs774650640
- Type
- single nucleotide variant
- Location
- chr11:32392739 (GRCh38)
- Gene constraint
- LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 52.09 · 31 PDB
- Residue 427
- a β-strand
Similar variants
- WT1 p.Gln427Pro Uncertain significance ★★ same residue
- WT1 p.Gln427His 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-gln427 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown