Is WNT4 p.Ser32= (c.96G>A) pathogenic?

WNT4 p.Ser32= (c.96G>A) is classified Likely benign in WNT4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.193%, amr); Associated with mullerian aplasia and hyperandrogenism.

What condition is associated with WNT4 p.Ser32= (c.96G>A)?

WNT4 p.Ser32= (c.96G>A) is associated with mullerian aplasia and hyperandrogenism, SERKAL syndrome (ClinVar).

How common is WNT4 p.Ser32= (c.96G>A) in the general population?

WNT4 p.Ser32= (c.96G>A) is rare (popmax 0.193%, amr) (gnomAD).

WNT4 p.Ser32=

c.96G>A · rs144407094 · VCV767291

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.193%, amr)

Conditions

mullerian aplasia and hyperandrogenism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.06	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -3.8
Overall
CADD	1.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.193% Admixed American · 116/60,030 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.025% 404/1,613,876 alleles · rare exomes 324/1,461,618 · genomes 80/152,258 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.193%	517
Middle Eastern	0.165%	606
Remaining individualsnot grpmax-eligible	0.056%	1,786
South Asian	0.0318%	3,141
African / African-American	0.0173%	5,771
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,922
European (non-Finnish)	0.0162%	6,178
East Asian	0.0111%	8,971

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: WNT4
Protein: p.Ser32=
Coding: c.96G>A
MANE Select: NM_030761
dbSNP: rs144407094
Type: single nucleotide variant
Location: chr1:22129833 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 91.41

Full WNT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mullerian aplasia and hyperandrogenism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: SERKAL syndrome

Similar variants

WNT4 p.Ala114Ser Uncertain significance ★★ ⚠ same condition
WNT4 p.Ala223Thr Uncertain significance ★★ ⚠ same condition
WNT4 p.Arg126Gln Uncertain significance ★★ ⚠ same condition
WNT4 p.Arg126Trp Uncertain significance ★★ ⚠ same condition
WNT4 p.Arg247Cys Uncertain significance ★★ same condition
WNT4 p.Arg285His Uncertain significance ★★ ⚠ same condition
WNT4 p.Arg294His Uncertain significance ★★ ⚠ same condition
WNT4 p.Arg86His Uncertain significance ★★ ⚠ same condition

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/wnt4-p-ser32 (accessed [today's date]).

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