Is WDR35 p.Pro351= (c.1053T>C) pathogenic?

WDR35 p.Pro351= (c.1053T>C) is classified Conflicting classifications of pathogenicity in WDR35 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-09-16). Rare (popmax 0.281%, eas); Associated with cranioectodermal dysplasia 2.

What condition is associated with WDR35 p.Pro351= (c.1053T>C)?

WDR35 p.Pro351= (c.1053T>C) is associated with cranioectodermal dysplasia 2, short-rib thoracic dysplasia 7 with or without polydactyly (ClinVar).

How common is WDR35 p.Pro351= (c.1053T>C) in the general population?

WDR35 p.Pro351= (c.1053T>C) is rare (popmax 0.281%, eas) (gnomAD).

WDR35 p.Pro351=

c.1053T>C · rs74385826 · VCV333398

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.281%, eas)

Conditions

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 -1.6	GERP -2.9
Overall
CADD	6.097	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% East Asian · 126/44,848 alleles

Filtering AF 0.241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.226%

Overall 0.00886% 143/1,613,946 alleles · rare exomes 132/1,461,640 · genomes 11/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.281%	356
Remaining individualsnot grpmax-eligible	0.0096%	10,417
South Asian	0.00439%	22,764
European (non-Finnish)	0.000593%	168,558

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.Pro351=
Coding: c.1053T>C
MANE Select: NM_020779
dbSNP: rs74385826
Type: single nucleotide variant
Location: chr2:19966865 (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

cranioectodermal dysplasia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short-rib thoracic dysplasia 7 with or without polydactyly

Similar variants

WDR35 p.Pro351Ala Conflicting classifications of pathogenicity ★ ⚠ 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-pro351 (accessed [today's date]).

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