WFS1 p.Phe343=
c.1029C>T · VCV3715358
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.024 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.6, phastCons 0.81 |
| Overall | ||
| CADD | 7.712 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,996 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000372%
6/1,613,944 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,999 |
| African / African-American | 0.00133% | 74,916 |
| European (non-Finnish) | 8.47e-05% | 1,179,954 |
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.Phe343=
- Coding
- c.1029C>T
- MANE Select
- NM_006005
- Type
- single nucleotide variant
- Location
- chr4:6300824 (GRCh38)
- Gene constraint
- LOEUF 1.64 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.85
Similar variants
- WFS1 p.Phe343Leu Uncertain significance ★ ⚠ same residue
- WFS1 p.Phe343Ala 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
- 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-phe343 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown