Is WNT3A p.Arg84= (c.252C>T) pathogenic?

WNT3A p.Arg84= (c.252C>T) is classified Likely benign in WNT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Ultra-rare (popmax 0.0217%, amr).

How common is WNT3A p.Arg84= (c.252C>T) in the general population?

WNT3A p.Arg84= (c.252C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

WNT3A p.Arg84=

c.252C>T · rs756167532 · VCV2740069

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -1.2, phastCons 0.4
Overall
CADD	7.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/60,012 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000806% 13/1,613,842 alleles · ultra-rare exomes 12/1,461,622 · genomes 1/152,220 · 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.Arg84=
Coding: c.252C>T
MANE Select: NM_033131
dbSNP: rs756167532
Type: single nucleotide variant
Location: chr1:228022847 (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.Arg84Cys Uncertain significance ★ ⚠ same residue
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

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-arg84 (accessed [today's date]).

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