WDR35 p.Pro222=
c.666T>A · rs987346249 · VCV471485
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 -6.1 | GERP -3.5 |
| Overall | ||
| CADD | 0.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,926 alleles
Overall
6.2e-05%
1/1,612,704 alleles · very rare
exomes 0/1,460,464 · genomes 1/152,240 · joint denominator
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.Pro222=
- Coding
- c.666T>A
- MANE Select
- NM_020779
- dbSNP
- rs987346249
- Type
- single nucleotide variant
- Location
- chr2:19974538 (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.Pro222Ala 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
- WDR35 p.Gln46Ter 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-pro222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown