AP5Z1 p.Ser587=
c.1761C>T · VCV3778192
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00274%, 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 -6.9 | GERP -3 |
| Overall | ||
| CADD | 5.966 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00274%
African / African-American · 2/73,124 alleles
Filtering AF
0.00098%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000808%
Overall
0.00129%
20/1,552,132 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00274% | 36,562 |
| European (non-Finnish) | 0.00157% | 63,786 |
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
- AP5Z1
- Protein
- p.Ser587=
- Coding
- c.1761C>T
- MANE Select
- NM_014855
- Type
- single nucleotide variant
- Location
- chr7:4789885 (GRCh38)
- Gene constraint
- LOEUF 1.641 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.32
Similar variants
- AP5Z1 p.Ser587Asn Uncertain significance ★ ⚠ same residue
- AP5Z1 c.1312-2A>G Pathogenic/Likely pathogenic ★★ same type
- AP5Z1 c.1707+1G>A Likely pathogenic ★★ same type
- AP5Z1 c.1806-1G>C Likely pathogenic ★★ same type
- AP5Z1 p.Arg138Ter Pathogenic/Likely pathogenic ★★ same type
- AP5Z1 p.Arg310Ter Pathogenic/Likely pathogenic ★★ same type
- AP5Z1 p.Arg311Ter Pathogenic/Likely pathogenic ★★ same type
- AP5Z1 p.Arg345Ter 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/ap5z1-p-ser587 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown