Is WNT10A p.Ser366Arg (c.1098C>A) pathogenic?

WNT10A p.Ser366Arg (c.1098C>A) is classified Uncertain significance in WNT10A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely pathogenic (0.8327); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with WNT10A p.Ser366Arg (c.1098C>A)?

WNT10A p.Ser366Arg (c.1098C>A) is associated with Inborn genetic diseases (ClinVar).

How common is WNT10A p.Ser366Arg (c.1098C>A) in the general population?

WNT10A p.Ser366Arg (c.1098C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WNT10A p.Ser366Arg (c.1098C>A)?

AlphaMissense predicts likely pathogenic (score 0.8327) — an in-silico prediction, not a clinical call.

WNT10A p.Ser366Arg

c.1098C>A · VCV3817321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8327 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,595,480)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8327	likely pathogenic
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -13.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.098	GERP -3.9, phastCons 0.002
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,595,480). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: WNT10A
Protein: p.Ser366Arg
Coding: c.1098C>A
MANE Select: NM_025216
Type: single nucleotide variant
Location: chr2:218893115 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.36
Residue 366: a disulfide bond; a UniProt-annotated variant site (in sthag4); a UniProt-annotated variant site (found in patients with dental anomalies; uncertain significance)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WNT10A p.Ser366= Likely benign ★ same residue
WNT10A p.Arg248Ter Pathogenic ★★ same condition
WNT10A p.Ala288Thr Uncertain significance ★★ ⚠ same condition
WNT10A p.Arg13Pro Uncertain significance ★★ ⚠ same condition
WNT10A p.Arg223Ser Uncertain significance ★★ ⚠ same condition
WNT10A p.Arg260Gln Uncertain significance ★★ ⚠ same condition
WNT10A p.Arg388Cys Uncertain significance ★★ ⚠ same condition
WNT10A p.Gly316Arg Uncertain significance ★★ ⚠ 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-ser366arg (accessed [today's date]).

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