AP3B2 p.Ser589=
c.1767C>A · rs776921804 · VCV1442192
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0317%, amr)
Conditions
1
developmental and epileptic encephalopathy, 48
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 -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.058 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0317%
Admixed American · 19/60,006 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.00403%
65/1,613,900 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0317% | 3,158 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,808 |
| European (non-Finnish) | 0.00314% | 31,889 |
| African / African-American | 0.00133% | 74,930 |
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
- AP3B2
- Protein
- p.Ser589=
- Coding
- c.1767C>A
- MANE Select
- NM_001278512
- dbSNP
- rs776921804
- Type
- single nucleotide variant
- Location
- chr15:82666832 (GRCh38)
- Gene constraint
- LOEUF 0.52 · pLI 0.22 (gnomAD)
- Structure
- AlphaFold pLDDT 75.73
Similar variants
- AP3B2 p.Arg977Ter Pathogenic ★★ same condition
- AP3B2 p.Gln839Ter Pathogenic/Likely pathogenic ★★ same condition
- AP3B2 c.1110+3G>C Uncertain significance ★★ same condition
- AP3B2 p.Ala1098Asp Uncertain significance ★★ ⚠ same condition
- AP3B2 p.Ala546Pro Uncertain significance ★★ ⚠ same condition
- AP3B2 p.Arg977Gln Uncertain significance ★★ ⚠ same condition
- AP3B2 p.Arg99Cys Uncertain significance ★★ ⚠ same condition
- AP3B2 p.Asn552Tyr Uncertain significance ★★ ⚠ same condition
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/ap3b2-p-ser589 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown