Is WNT3A p.Val91Ile (c.271G>A) pathogenic?

WNT3A p.Val91Ile (c.271G>A) is classified Uncertain significance in WNT3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-20). AlphaMissense: likely benign (0.0668); Ultra-rare (popmax 0.0165%, mid).

How common is WNT3A p.Val91Ile (c.271G>A) in the general population?

WNT3A p.Val91Ile (c.271G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about WNT3A p.Val91Ile (c.271G>A)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

WNT3A p.Val91Ile

c.271G>A · rs572229142 · VCV2217517

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -5.29	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 0.49	GERP -2.8, phastCons 0.016
Regional constraint	o/e 0.81	unconstrained · MANE · 52 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	0.893	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 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.00192% 31/1,613,052 alleles · ultra-rare exomes 25/1,460,732 · genomes 6/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
South Asian	0.00988%	10,117
East Asian	0.00891%	11,218
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,460
European (non-Finnish)	0.00127%	78,619

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: WNT3A
Protein: p.Val91Ile
Coding: c.271G>A
MANE Select: NM_033131
dbSNP: rs572229142
Type: single nucleotide variant
Location: chr1:228022866 (GRCh38)
Gene constraint: LOEUF 0.76 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62 · 4 PDB

Full WNT3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WNT3A p.Ala318Pro Uncertain significance ★★ ⚠ same type
WNT3A p.Arg141His Uncertain significance ★★ ⚠ same type
WNT3A p.Arg141Pro Uncertain significance ★★ ⚠ same type
WNT3A p.Arg322Gln Uncertain significance ★★ ⚠ same type
WNT3A p.Arg324Trp Uncertain significance ★★ ⚠ same type
WNT3A p.Arg82His Uncertain significance ★★ ⚠ same type
WNT3A p.Glu160Lys Uncertain significance ★★ ⚠ same type
WNT3A p.Glu68Lys Uncertain significance ★★ ⚠ same type

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/wnt3a-p-val91ile (accessed [today's date]).

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