Is WNT10A p.Asp166= (c.498C>T) pathogenic?

WNT10A p.Asp166= (c.498C>T) is classified Conflicting classifications of pathogenicity in WNT10A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-02). Ultra-rare (popmax 0.0117%, amr); Associated with tooth agenesis, selective, 4.

What condition is associated with WNT10A p.Asp166= (c.498C>T)?

WNT10A p.Asp166= (c.498C>T) is associated with tooth agenesis, selective, 4, Schöpf-Schulz-Passarge syndrome, odonto-onycho-dermal dysplasia (ClinVar).

How common is WNT10A p.Asp166= (c.498C>T) in the general population?

WNT10A p.Asp166= (c.498C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

WNT10A p.Asp166=

c.498C>T · rs143463683 · VCV334400

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

tooth agenesis, selective, 4

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 -2.8	GERP -4.4
Overall
CADD	4.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,998 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00167% 27/1,614,040 alleles · ultra-rare exomes 21/1,461,830 · genomes 6/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
South Asian	0.0022%	45,542
European (non-Finnish)	0.00153%	65,558

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: WNT10A
Protein: p.Asp166=
Coding: c.498C>T
MANE Select: NM_025216
dbSNP: rs143463683
Type: single nucleotide variant
Location: chr2:218890105 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.36
Residue 166: a UniProt-annotated variant site (in sthag4)

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

Disease context

tooth agenesis, selective, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Schöpf-Schulz-Passarge syndrome odonto-onycho-dermal dysplasia

Similar variants

WNT10A p.Asp166fs Likely pathogenic ★ 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-asp166 (accessed [today's date]).

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