Is WNT3A p.Pro30Ser (c.88C>T) pathogenic?

WNT3A p.Pro30Ser (c.88C>T) is classified Uncertain significance in WNT3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). AlphaMissense: likely benign (0.0749); Ultra-rare (popmax 0.0117%, amr).

How common is WNT3A p.Pro30Ser (c.88C>T) in the general population?

WNT3A p.Pro30Ser (c.88C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about WNT3A p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

WNT3A p.Pro30Ser

c.88C>T · rs1329090456 · VCV1938455

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -4.64	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 4.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 52 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	17.52	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 0.0117% Admixed American · 7/59,984 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000434% 7/1,613,272 alleles · ultra-rare exomes 6/1,461,094 · genomes 1/152,178 · 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: WNT3A
Protein: p.Pro30Ser
Coding: c.88C>T
MANE Select: NM_033131
dbSNP: rs1329090456
Type: single nucleotide variant
Location: chr1:228022683 (GRCh38)
Gene constraint: LOEUF 0.76 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62 · 4 PDB
Residue 30: an α-helix

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-pro30ser (accessed [today's date]).

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