CPZ p.Arg522=
c.1566G>T · rs116114355 · VCV783318
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.42%, afr)
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 -2.3 | GERP -3.9 |
| Overall | ||
| CADD | 0.704 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.42%
African / African-American · 1,067/75,056 alleles
Filtering AF
1.35%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.32%
Overall
0.0738%
1,192/1,614,128 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.42% | 70 |
| Admixed American | 0.0766% | 1,305 |
| Remaining individualsnot grpmax-eligible | 0.0688% | 1,454 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.00288% | 34,707 |
| South Asian | 0.0011% | 91,080 |
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
- CPZ
- Protein
- p.Arg522=
- Coding
- c.1566G>T
- MANE Select
- NM_001014447
- dbSNP
- rs116114355
- Type
- single nucleotide variant
- Location
- chr4:8618491 (GRCh38)
- Gene constraint
- LOEUF 1.966 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.33
Similar variants
- CPZ p.Arg522Gln Uncertain significance ★ ⚠ same residue
- CPZ p.Gln317Ter Uncertain significance ★★ same type
- CPZ c.1068+9C>T Benign ★★ same type
- CPZ c.1604-8G>T Benign ★★ same type
- CPZ p.Arg647= Likely benign ★★ same type
- CPZ p.Asn250= Benign ★★ same type
- CPZ p.Gln263Arg Benign ★★ ⚠ same type
- CPZ p.Pro618= Benign ★★ 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/cpz-p-arg522 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown