WFS1 p.Pro504=
c.1512G>C · rs201684148 · VCV1970699
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -0.62 | GERP -2.9, phastCons 0.013 |
| Overall | ||
| CADD | 0.291 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,028 alleles
Overall
0.000124%
2/1,611,332 alleles · very rare
exomes 2/1,459,042 · genomes 0/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,028 |
| European (non-Finnish) | 8.47e-05% | 1,180,008 |
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.Pro504=
- Coding
- c.1512G>C
- MANE Select
- NM_006005
- dbSNP
- rs201684148
- Type
- single nucleotide variant
- Location
- chr4:6301307 (GRCh38)
- Gene constraint
- LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.85
- Residue 504
- a UniProt-annotated variant site (in wfs1)
Similar variants
- WFS1 p.Pro504Leu Pathogenic/Likely pathogenic ★★ same residue
- WFS1 p.Pro504Thr Uncertain significance ★★ ⚠ same residue
- WFS1 p.Pro504Arg Uncertain significance ★ ⚠ same residue
- WFS1 p.Pro504Gln Uncertain significance ★ ⚠ same residue
- WFS1 p.Pro504Ser Uncertain significance ★ ⚠ 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
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-pro504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown