WDR35 p.Gln537Ter
c.1609C>T · rs1416766008 · VCV2951856
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
cranioectodermal dysplasia 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 15 of 27 |
| Splicing | ||
| SpliceAI | Δ0.35 | donor loss, 25 bp away · masked 0 · deltas |
| Pangolin | Δ0.47 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 39.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- WDR35
- Protein
- p.Gln537Ter
- Coding
- c.1609C>T
- MANE Select
- NM_020779
- dbSNP
- rs1416766008
- Type
- single nucleotide variant
- Location
- chr2:19946486 (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 537
- a UniProt-annotated variant site (in srtd7; chondrocyte cell lines from the patient show a reduction of cilia indicating a defect in ciliogenesis); a β-strand
Similar variants
- WDR35 p.Gln537Glu 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-gln537ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown