Is WNT10A p.Arg7= (c.21C>T) pathogenic?

WNT10A p.Arg7= (c.21C>T) is classified Likely benign in WNT10A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). Very rare (popmax 0.000171%, nfe); Associated with odonto-onycho-dermal dysplasia.

What condition is associated with WNT10A p.Arg7= (c.21C>T)?

WNT10A p.Arg7= (c.21C>T) is associated with odonto-onycho-dermal dysplasia, tooth agenesis, selective, 4 (ClinVar).

How common is WNT10A p.Arg7= (c.21C>T) in the general population?

WNT10A p.Arg7= (c.21C>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

How is Odonto-onycho-dermal dysplasia inherited?

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

WNT10A p.Arg7=

c.21C>T · rs964401766 · VCV1925254

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

odonto-onycho-dermal dysplasia

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 0.065, phastCons 1
Overall
CADD	12.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,168,946 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,591,632 alleles · very rare exomes 2/1,439,310 · genomes 0/152,322 · 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: WNT10A
Protein: p.Arg7=
Coding: c.21C>T
MANE Select: NM_025216
dbSNP: rs964401766
Type: single nucleotide variant
Location: chr2:218881016 (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 p.Arg7Ser 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-arg7 (accessed [today's date]).

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