Is WNT3 p.Pro180= (c.540G>A) pathogenic?

WNT3 p.Pro180= (c.540G>A) is classified Likely benign in WNT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-17). Ultra-rare (popmax 0.0329%, mid).

How common is WNT3 p.Pro180= (c.540G>A) in the general population?

WNT3 p.Pro180= (c.540G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

WNT3 p.Pro180=

c.540G>A · rs768238279 · VCV2868500

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -10	GERP -7.9
Overall
CADD	0.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00062% 10/1,613,072 alleles · ultra-rare exomes 8/1,460,842 · genomes 2/152,230 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
African / African-American	0.00267%	37,466
South Asian	0.0022%	45,531
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.000254%	393,298

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: WNT3
Protein: p.Pro180=
Coding: c.540G>A
MANE Select: NM_030753
dbSNP: rs768238279
Type: single nucleotide variant
Location: chr17:46769831 (GRCh38)

Full WNT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/wnt3-p-pro180 (accessed [today's date]).

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