WDR35 p.Ala166=
c.498G>A · rs150578416 · VCV2923863
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
Conditions
2
cranioectodermal dysplasia 2
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 -2 | GERP -3.3 |
| Overall | ||
| CADD | 8.222 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,084 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00155%
25/1,613,892 alleles · very rare
exomes 23/1,461,764 · genomes 2/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,181 |
| European (non-Finnish) | 0.00161% | 62,103 |
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
- WDR35
- Protein
- p.Ala166=
- Coding
- c.498G>A
- MANE Select
- NM_020779
- dbSNP
- rs150578416
- Type
- single nucleotide variant
- Location
- chr2:19975602 (GRCh38)
- Gene constraint
- LOEUF 0.776 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 4 PDB
Similar variants
- WDR35 p.Ala166Val Uncertain significance ★★ ⚠ same residue
- WDR35 p.Ala166Thr Uncertain significance ★ ⚠ same residue
- WDR35 c.1255+1G>A Pathogenic/Likely pathogenic ★★ same condition
- WDR35 c.2415-2A>G Likely pathogenic ★★ same condition
- WDR35 p.Arg332Ter Pathogenic ★★ same condition
- WDR35 p.Arg461Ter Pathogenic ★★ same condition
- WDR35 p.Arg564Ter Pathogenic/Likely pathogenic ★★ same condition
- WDR35 p.Arg582Ter Pathogenic/Likely pathogenic ★★ 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/wdr35-p-ala166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown