WAC p.Asp273=
c.819T>C · VCV4847178
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 3.5 | GERP 0.56, phastCons 1 |
| Overall | ||
| CADD | 10.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00275%
Overall
0.00341%
55/1,614,056 alleles · ultra-rare
exomes 51/1,461,872 · genomes 4/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| European (non-Finnish) | 0.00398% | 25,107 |
| Admixed American | 0.00333% | 30,000 |
| Finnishnot grpmax-eligible | 0.00156% | 64,030 |
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.Asp273=
- Coding
- c.819T>C
- MANE Select
- NM_016628
- Type
- single nucleotide variant
- Location
- chr10:28595941 (GRCh38)
- Gene constraint
- LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.71
- Residue 273
- the 'disordered' region; a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic)
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-asp273 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown