WFS1 p.Asp729=
c.2187C>T · rs368554932 · VCV2147442
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0417%, sas)
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 2.1 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 6.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0417%
South Asian · 38/91,078 alleles
Filtering AF
0.0312%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0275%
Overall
0.00273%
44/1,612,780 alleles · ultra-rare
exomes 44/1,460,404 · genomes 0/152,376 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0417% | 2,397 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.00167% | 60,000 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 0.000254% | 393,309 |
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
- WFS1
- Protein
- p.Asp729=
- Coding
- c.2187C>T
- MANE Select
- NM_006005
- dbSNP
- rs368554932
- Type
- single nucleotide variant
- Location
- chr4:6301982 (GRCh38)
- Gene constraint
- LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.85
Similar variants
- WFS1 p.Asp729Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
- WFS1 c.233-1G>C Pathogenic/Likely pathogenic ★★ same type
- WFS1 c.316-2A>G Pathogenic ★★ same type
- WFS1 c.460+1G>A Pathogenic ★★ same type
- WFS1 c.631+1G>A Likely pathogenic ★★ same type
- WFS1 c.861+1G>A Pathogenic/Likely pathogenic ★★ same type
- WFS1 c.861+2T>C Pathogenic ★★ same type
- WFS1 p.Ala126Thr Pathogenic/Likely pathogenic ★★ same type
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/wfs1-p-asp729 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown