Is WNT10A p.Pro327= (c.981G>T) pathogenic?

WNT10A p.Pro327= (c.981G>T) is classified Likely benign in WNT10A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). Very rare (popmax 0.00119%, sas); Associated with odonto-onycho-dermal dysplasia.

What condition is associated with WNT10A p.Pro327= (c.981G>T)?

WNT10A p.Pro327= (c.981G>T) is associated with odonto-onycho-dermal dysplasia, tooth agenesis, selective, 4 (ClinVar).

How common is WNT10A p.Pro327= (c.981G>T) in the general population?

WNT10A p.Pro327= (c.981G>T) is very rare (popmax 0.00119%, sas) (gnomAD).

How is Odonto-onycho-dermal dysplasia inherited?

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

WNT10A p.Pro327=

c.981G>T · rs753905653 · VCV2095186

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Conditions

odonto-onycho-dermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4
Overall
CADD	5.228	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,148 alleles

Overall 7.2e-05% 1/1,388,698 alleles · very rare

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.Pro327=
Coding: c.981G>T
MANE Select: NM_025216
dbSNP: rs753905653
Type: single nucleotide variant
Location: chr2:218892998 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.36
Residue 327: the 'disordered' region; a UniProt-annotated variant site (in sthag4)

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 p.Pro327Gln Uncertain significance ★ ⚠ same residue
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

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-pro327 (accessed [today's date]).

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