Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.67%, afr) — too common for a highly-penetrant pathogenic allele
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 4.1 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 11.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.67%
African / African-American · 4,257/75,014 alleles
Filtering AF
5.53%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.47%
Overall
0.522%
8,426/1,614,124 alleles · common
exomes 5,509/1,461,854 · genomes 2,917/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.67% | 18 |
| Middle Eastern | 2.47% | 40 |
| Admixed American | 1.69% | 59 |
| Remaining individualsnot grpmax-eligible | 1.03% | 97 |
| Ashkenazi Jewishnot grpmax-eligible | 0.959% | 104 |
| European (non-Finnish) | 0.173% | 579 |
| South Asian | 0.0428% | 2,335 |
| East Asian | 0.00223% | 44,870 |
| Finnishnot grpmax-eligible | 0.00156% | 64,026 |
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.Ser452=
- Coding
- c.1356T>G
- MANE Select
- NM_016628
- dbSNP
- rs2232792
- Type
- single nucleotide variant
- Location
- chr10:28611841 (GRCh38)
- Gene constraint
- LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.71
- Residue 452
- a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic); the 'disordered' region
Similar variants
- WAC c.1437+1G>A Pathogenic/Likely pathogenic ★★ same type
- WAC c.1746+2T>C Pathogenic ★★ same type
- WAC c.381+1G>T Likely pathogenic ★★ same type
- WAC p.Arg151Ter Pathogenic ★★ same type
- WAC p.Arg47Ter Pathogenic ★★ same type
- WAC p.Arg513Ter Pathogenic ★★ same type
- WAC p.Arg550Ter Pathogenic ★★ same type
- WAC p.Arg613Ter Pathogenic/Likely pathogenic ★★ 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/wac-p-ser452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown