Is WNT4 p.Pro96Arg (c.287C>G) pathogenic?

WNT4 p.Pro96Arg (c.287C>G) is classified Uncertain significance in WNT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: ambiguous (0.5076); Very rare (popmax 0.00549%, sas); Associated with Inborn genetic diseases.

What condition is associated with WNT4 p.Pro96Arg (c.287C>G)?

WNT4 p.Pro96Arg (c.287C>G) is associated with Inborn genetic diseases (ClinVar).

How common is WNT4 p.Pro96Arg (c.287C>G) in the general population?

WNT4 p.Pro96Arg (c.287C>G) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about WNT4 p.Pro96Arg (c.287C>G)?

AlphaMissense predicts ambiguous (score 0.5076) — an in-silico prediction, not a clinical call.

WNT4 p.Pro96Arg

c.287C>G · VCV4202051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5076 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5076	ambiguous
REVEL	0.495	indeterminate
SaProt	LLR -11.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 9,752 bp · p 3.2e-10 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,082 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000744% 12/1,613,542 alleles · very rare exomes 10/1,461,334 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000508%	196,670

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: WNT4
Protein: p.Pro96Arg
Coding: c.287C>G
MANE Select: NM_030761
Type: single nucleotide variant
Location: chr1:22129642 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 91.41

Full WNT4 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

WNT4 p.Pro96= Likely benign ★ same residue
WNT4 p.Arg86His Uncertain significance ★★ ⚠ same condition
WNT4 p.Asp304Asn Uncertain significance ★★ ⚠ same condition
WNT4 p.Gly99Ser Uncertain significance ★★ ⚠ same condition
WNT4 p.Ala318Val Uncertain significance ★ ⚠ same condition
WNT4 p.Arg228Cys Uncertain significance ★ ⚠ same condition
WNT4 p.Arg339Gln Uncertain significance ★ ⚠ same condition
WNT4 p.Arg343Gln 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/wnt4-p-pro96arg (accessed [today's date]).

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