Is WNT3A p.Phe81= (c.243C>T) pathogenic?

WNT3A p.Phe81= (c.243C>T) is classified Likely benign in WNT3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). Very rare (popmax 0.00133%, afr).

How common is WNT3A p.Phe81= (c.243C>T) in the general population?

WNT3A p.Phe81= (c.243C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

WNT3A p.Phe81=

c.243C>T · VCV3612369

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 3.1	GERP 1.9, phastCons 1
Overall
CADD	11.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,074 alleles

Overall 6.2e-05% 1/1,613,950 alleles · very rare exomes 1/1,461,574 · genomes 0/152,376 · 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.Phe81=
Coding: c.243C>T
MANE Select: NM_033131
Type: single nucleotide variant
Location: chr1:228022838 (GRCh38)
Gene constraint: LOEUF 0.76 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62 · 4 PDB
Residue 81: a turn

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

Similar variants

WNT3A p.Phe81Leu 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-phe81 (accessed [today's date]).

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