Is WNT10A p.Pro320Ser (c.958C>T) pathogenic?

WNT10A p.Pro320Ser (c.958C>T) is classified Uncertain significance in WNT10A (ClinVar, Single submitter, 2 submitters; last evaluated 2018-06-11). AlphaMissense: likely benign (0.0692); Very rare (popmax 8.99e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with WNT10A p.Pro320Ser (c.958C>T)?

WNT10A p.Pro320Ser (c.958C>T) is associated with Inborn genetic diseases, Schöpf-Schulz-Passarge syndrome (ClinVar).

How common is WNT10A p.Pro320Ser (c.958C>T) in the general population?

WNT10A p.Pro320Ser (c.958C>T) is very rare (popmax 8.99e-05%, nfe) (gnomAD).

What do computational predictors say about WNT10A p.Pro320Ser (c.958C>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

WNT10A p.Pro320Ser

c.958C>T · rs1944673587 · VCV985708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.99e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -0.3, phastCons 0.96
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	15.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 8.99e-05% European (non-Finnish) · 1/1,112,668 alleles

Overall 6.87e-05% 1/1,456,594 alleles · very rare exomes 1/1,304,452 · genomes 0/152,142 · 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.Pro320Ser
Coding: c.958C>T
MANE Select: NM_025216
dbSNP: rs1944673587
Type: single nucleotide variant
Location: chr2:218892975 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.36
Residue 320: 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

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

Also linked: Schöpf-Schulz-Passarge syndrome

Similar variants

WNT10A p.Pro320Arg 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-pro320ser (accessed [today's date]).

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