Is WNT10A p.Pro53= (c.159C>T) pathogenic?

WNT10A p.Pro53= (c.159C>T) is classified Likely benign in WNT10A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). Ultra-rare (popmax 0.0267%, afr); Associated with odonto-onycho-dermal dysplasia.

What condition is associated with WNT10A p.Pro53= (c.159C>T)?

WNT10A p.Pro53= (c.159C>T) is associated with odonto-onycho-dermal dysplasia, tooth agenesis, selective, 4 (ClinVar).

How common is WNT10A p.Pro53= (c.159C>T) in the general population?

WNT10A p.Pro53= (c.159C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

How is Odonto-onycho-dermal dysplasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

WNT10A p.Pro53=

c.159C>T · rs143421847 · VCV1082175

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Conditions

odonto-onycho-dermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.8
Overall
CADD	0.919	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,902 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0134% 216/1,614,034 alleles · ultra-rare exomes 202/1,461,858 · genomes 14/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,745
European (non-Finnish)	0.0164%	6,083
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: WNT10A
Protein: p.Pro53=
Coding: c.159C>T
MANE Select: NM_025216
dbSNP: rs143421847
Type: single nucleotide variant
Location: chr2:218882206 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.36

Full WNT10A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

odonto-onycho-dermal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tooth agenesis, selective, 4

For Odonto-onycho-dermal dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

WNT10A c.113+1G>A Likely pathogenic ★★ same condition
WNT10A c.113+1G>T Likely pathogenic ★★ same condition
WNT10A c.376+1G>A Pathogenic ★★ same condition
WNT10A p.Ala131Thr Pathogenic/Likely pathogenic ★★ same condition
WNT10A p.Ala297Thr Likely pathogenic ★★ same condition
WNT10A p.Arg104Cys Pathogenic/Likely pathogenic ★★ same condition
WNT10A p.Arg128Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
WNT10A p.Arg13Ter 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/wnt10a-p-pro53 (accessed [today's date]).

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