Is WDR35 p.Asp244= (c.732C>T) pathogenic?

WDR35 p.Asp244= (c.732C>T) is classified Likely benign in WDR35 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Very rare (popmax 0.000255%, nfe); Associated with short-rib thoracic dysplasia 7 with or without polydactyly.

How common is WDR35 p.Asp244= (c.732C>T) in the general population?

WDR35 p.Asp244= (c.732C>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

WDR35 p.Asp244=

Q: What condition is associated with WDR35 p.Asp244= (c.732C>T)?

WDR35 p.Asp244= (c.732C>T) is associated with short-rib thoracic dysplasia 7 with or without polydactyly, cranioectodermal dysplasia 2 (ClinVar).

c.732C>T · rs990193280 · VCV2127447

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,175,238 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000187% 3/1,601,794 alleles · very rare exomes 2/1,449,900 · genomes 1/151,894 · 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.Asp244=
Coding: c.732C>T
MANE Select: NM_020779
dbSNP: rs990193280
Type: single nucleotide variant
Location: chr2:19974472 (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.Asp244Gly 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-asp244 (accessed [today's date]).

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