WDR35 p.Pro874=
c.2622A>C · rs766138190 · VCV1652518
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00941%, nfe)
Conditions
2
short-rib thoracic dysplasia 7 with or without polydactyly
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 -1.7 | |
| Overall | ||
| CADD | 6.614 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00941%
European (non-Finnish) · 111/1,179,974 alleles
Filtering AF
0.00791%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00744%
Overall
0.00719%
116/1,613,942 alleles · very rare
exomes 113/1,461,676 · genomes 3/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00941% | 10,630 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| Admixed American | 0.00167% | 59,998 |
| African / African-American | 0.00133% | 74,950 |
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.Pro874=
- Coding
- c.2622A>C
- MANE Select
- NM_020779
- dbSNP
- rs766138190
- Type
- single nucleotide variant
- Location
- chr2:19933437 (GRCh38)
- Gene constraint
- LOEUF 0.776 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 4 PDB
- Residue 874
- an α-helix; a UniProt-annotated variant site (in srtd7; chondrocyte cell lines from the patient show a reduction of cilia indicating a defect in ciliogenesis)
Similar variants
- 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
- WDR35 p.Gly69Asp 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-pro874 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown