WDR81 p.Phe495=
c.1485C>T · VCV3388569
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.111%, 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 1.8 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 5.601 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.111%
African / African-American · 81/73,174 alleles
Filtering AF
0.0913%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0841%
Overall
0.00755%
117/1,550,466 alleles · rare
exomes 77/1,398,198 · genomes 40/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.111% | 903 |
| Middle Eastern | 0.0167% | 5,994 |
| Remaining individualsnot grpmax-eligible | 0.00832% | 12,025 |
| European (non-Finnish) | 0.00244% | 40,964 |
| Admixed American | 0.00196% | 51,004 |
| South Asian | 0.00119% | 84,058 |
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
- WDR81
- Protein
- p.Phe495=
- Coding
- c.1485C>T
- MANE Select
- NM_001163809
- Type
- single nucleotide variant
- Location
- chr17:1726444 (GRCh38)
- Gene constraint
- LOEUF 0.817 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.23
- Residue 495
- the beach domain; the 'necessary and sufficient for the interaction with sqstm1' region
Similar variants
- WDR81 p.Arg1333Ter Pathogenic/Likely pathogenic ★★ same type
- WDR81 p.Arg1779Ter Pathogenic ★★ same type
- WDR81 p.Arg397Ter Likely pathogenic ★★ same type
- WDR81 p.Gln1096Ter Pathogenic ★★ same type
- WDR81 p.Pro856Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- WDR81 p.Tyr1257Ter Pathogenic/Likely pathogenic ★★ same type
- WDR81 p.Tyr1281Ter Pathogenic/Likely pathogenic ★★ same type
- WDR81 p.Ala1015Thr Uncertain significance ★★ ⚠ 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/wdr81-p-phe495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown