WFS1 p.Pro7=
c.21G>A · rs372928810 · VCV2896241
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, mid)
Conditions
1
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 -3.8 | GERP -2.4 |
| Overall | ||
| CADD | 0.442 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
Middle Eastern · 1/5,966 alleles
Filtering AF
0.000299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000216%
Overall
0.000899%
14/1,557,916 alleles · ultra-rare
exomes 14/1,405,600 · genomes 0/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0168% | 5,966 |
| East Asian | 0.00239% | 41,780 |
| Admixed American | 0.00193% | 51,862 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,376 |
| African / African-American | 0.00136% | 73,678 |
| South Asian | 0.00118% | 84,658 |
| European (non-Finnish) | 0.000695% | 143,870 |
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.Pro7=
- Coding
- c.21G>A
- MANE Select
- NM_006005
- dbSNP
- rs372928810
- Type
- single nucleotide variant
- Location
- chr4:6277476 (GRCh38)
- Gene constraint
- LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.85
- Residue 7
- the 'interaction with atp6v1a' region; the 'disordered' region
Similar variants
- WFS1 p.Pro7Leu Uncertain significance ★★ ⚠ same residue
- WFS1 p.Pro7Ser Uncertain significance ★★ ⚠ same residue
- WFS1 p.Arg42Ter Pathogenic/Likely pathogenic ★★ same condition
- WFS1 p.Arg629Trp Pathogenic ★★ ⚠ same condition
- WFS1 p.Cys647Ter Pathogenic/Likely pathogenic ★★ same condition
- WFS1 p.Leu829Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
- WFS1 p.Ala214Val Uncertain significance ★★ ⚠ same condition
- WFS1 p.Ala275Gly Uncertain significance ★★ ⚠ 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/wfs1-p-pro7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown