AP3B2 p.Pro867=
c.2601G>A · rs372227718 · VCV1634121
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0614%, 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 1.2 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 10.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0614%
African / African-American · 46/74,946 alleles
Filtering AF
0.0472%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0423%
Overall
0.00708%
114/1,609,252 alleles · ultra-rare
exomes 81/1,457,030 · genomes 33/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0614% | 1,629 |
| Finnishnot grpmax-eligible | 0.0422% | 2,367 |
| Admixed American | 0.0218% | 4,591 |
| Remaining individualsnot grpmax-eligible | 0.00642% | 15,565 |
| European (non-Finnish) | 0.00204% | 49,093 |
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.Pro867=
- Coding
- c.2601G>A
- MANE Select
- NM_001278512
- dbSNP
- rs372227718
- Type
- single nucleotide variant
- Location
- chr15:82663130 (GRCh38)
- Gene constraint
- LOEUF 0.52 · pLI 0.22 (gnomAD)
- Structure
- AlphaFold pLDDT 75.73
Similar variants
- AP3B2 p.Pro867Leu Uncertain significance ★★ ⚠ same residue
- AP3B2 p.Pro867Ser Uncertain significance ★ ⚠ same residue
- AP3B2 c.114-1G>A Likely pathogenic ★★ same type
- AP3B2 p.Arg977Ter Pathogenic ★★ same type
- AP3B2 p.Gln839Ter Pathogenic/Likely pathogenic ★★ same type
- AP3B2 c.1110+3G>C Uncertain significance ★★ same type
- AP3B2 c.1853-5C>A Uncertain significance ★★ same type
- AP3B2 c.2834-3C>A Uncertain significance ★★ 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/ap3b2-p-pro867 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown