WAC p.Arg622=
c.1866A>G · rs34120502 · VCV709566
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.49%, afr)
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 5.2 | GERP -0.68, phastCons 1 |
| Overall | ||
| CADD | 11.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.49%
African / African-American · 3,295/73,326 alleles
Filtering AF
4.37%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.31%
Overall
0.244%
3,860/1,584,442 alleles · low-frequency
exomes 1,894/1,432,076 · genomes 1,966/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.49% | 22 |
| Remaining individualsnot grpmax-eligible | 0.34% | 294 |
| Admixed American | 0.326% | 307 |
| Middle Eastern | 0.137% | 729 |
| European (non-Finnish) | 0.0145% | 6,893 |
| South Asian | 0.0109% | 9,139 |
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.Arg622=
- Coding
- c.1866A>G
- MANE Select
- NM_016628
- dbSNP
- rs34120502
- Type
- single nucleotide variant
- Location
- chr10:28617776 (GRCh38)
- Gene constraint
- LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.71
- Residue 622
- a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic)
Similar variants
- WAC p.Arg622Ter Pathogenic/Likely pathogenic ★★ same residue
- WAC p.Arg622Gln Uncertain significance ★★ ⚠ same residue
- WAC p.Arg622fs Pathogenic ★ same residue
- 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
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-arg622 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown