Is WDR35 p.Ser266= (c.798C>T) pathogenic?

WDR35 p.Ser266= (c.798C>T) is classified Conflicting classifications of pathogenicity in WDR35 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-22). Ultra-rare (popmax 0.099%, mid); Associated with short-rib thoracic dysplasia 7 with or without polydactyly.

How common is WDR35 p.Ser266= (c.798C>T) in the general population?

WDR35 p.Ser266= (c.798C>T) is ultra-rare (popmax 0.099%, mid) (gnomAD).

WDR35 p.Ser266=

Q: What condition is associated with WDR35 p.Ser266= (c.798C>T)?

WDR35 p.Ser266= (c.798C>T) is associated with short-rib thoracic dysplasia 7 with or without polydactyly, cranioectodermal dysplasia 2 (ClinVar).

c.798C>T · rs141118263 · VCV333401

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Conditions

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 -4.3	GERP -3.2
Overall
CADD	2.911	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.0147% 237/1,614,168 alleles · ultra-rare exomes 229/1,461,878 · genomes 8/152,290 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
South Asian	0.0527%	1,898
Remaining individualsnot grpmax-eligible	0.0176%	5,683
European (non-Finnish)	0.0138%	7,239
Admixed American	0.005%	20,007
Finnishnot grpmax-eligible	0.00469%	21,338
African / African-American	0.004%	25,018

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.Ser266=
Coding: c.798C>T
MANE Select: NM_020779
dbSNP: rs141118263
Type: single nucleotide variant
Location: chr2:19973647 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 4 PDB

Full WDR35 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 7 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cranioectodermal dysplasia 2

Similar variants

WDR35 p.Ser266Gly Uncertain significance ★★ ⚠ same residue
WDR35 p.Ser266Asn 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-ser266 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown