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

WAC p.Ser32= (c.96G>A) is classified Likely benign in WAC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-01-18). Ultra-rare (popmax 0.0128%, nfe); Associated with WAC-related disorder.

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

WAC p.Ser32= (c.96G>A) is associated with WAC-related disorder (ClinVar).

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

WAC p.Ser32= (c.96G>A) is ultra-rare (popmax 0.0128%, nfe) (gnomAD).

WAC p.Ser32=

c.96G>A · rs201074071 · VCV3035983

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, nfe)

Conditions

WAC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.14	phastCons 0.72
Overall
CADD	11.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0128% European (non-Finnish) · 151/1,177,816 alleles

Filtering AF 0.0111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.0101% 163/1,609,400 alleles · ultra-rare exomes 154/1,457,578 · genomes 9/151,822 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0128%	7,800
Remaining individualsnot grpmax-eligible	0.00803%	12,447
African / African-American	0.00536%	18,640
Admixed American	0.00505%	19,801

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: WAC
Protein: p.Ser32=
Coding: c.96G>A
MANE Select: NM_016628
dbSNP: rs201074071
Type: single nucleotide variant
Location: chr10:28535579 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 32: the 'disordered' region

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

Disease context

WAC-related disorder

Similar variants

WAC p.Ser32Leu Uncertain significance ★ ⚠ same residue
WAC p.Gln170Ter Pathogenic ★★ same condition
WAC p.Ser222Tyr Uncertain significance ★★ ⚠ same condition
WAC p.Gln504Ter Likely pathogenic ★ same condition
WAC p.Ser279Ter Likely pathogenic ★ same condition
WAC p.Cys602Ser Uncertain significance ★ same condition
WAC p.Met598Val Uncertain significance ★ ⚠ same condition
WAC p.His530Arg 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/wac-p-ser32 (accessed [today's date]).

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