WFS1 p.Ser784=
c.2352C>T · rs373431795 · VCV1648149
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, afr)
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 -0.31 | GERP 1.3 |
| Overall | ||
| CADD | 2.311 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
African / African-American · 18/74,950 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.00149%
24/1,612,880 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.024% | 4,164 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,234 |
| Admixed American | 0.00167% | 60,010 |
| European (non-Finnish) | 0.000254% | 393,337 |
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.Ser784=
- Coding
- c.2352C>T
- MANE Select
- NM_006005
- dbSNP
- rs373431795
- Type
- single nucleotide variant
- Location
- chr4:6302147 (GRCh38)
- Gene constraint
- LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.85
Similar variants
- WFS1 p.Ser784Cys Uncertain significance ★ ⚠ same residue
- WFS1 p.Ser784Arg Likely benign ★ 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
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-ser784 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown