AP4B1 p.Pro80=
c.240A>G · rs34249695 · VCV157720
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.84%, afr)
Conditions
2
Inborn genetic diseases
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 -0.17 | GERP 0.97, phastCons 0.73 |
| Overall | ||
| CADD | 13.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.84%
African / African-American · 1,382/75,044 alleles
Filtering AF
1.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.73%
Overall
0.0961%
1,552/1,614,218 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.84% | 54 |
| Admixed American | 0.133% | 750 |
| Remaining individualsnot grpmax-eligible | 0.101% | 992 |
| Middle Eastern | 0.099% | 1,010 |
| East Asian | 0.00446% | 22,445 |
| South Asian | 0.00329% | 30,364 |
| European (non-Finnish) | 0.00136% | 73,752 |
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
- AP4B1
- Protein
- p.Pro80=
- Coding
- c.240A>G
- MANE Select
- NM_001253852
- dbSNP
- rs34249695
- Type
- single nucleotide variant
- Location
- chr1:113902736 (GRCh38)
- Gene constraint
- LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.56 · 5 PDB
Similar variants
- AP4B1 p.Pro80Leu Uncertain significance ★ ⚠ same residue
- AP4B1 c.114-2A>C Pathogenic ★★ same condition
- AP4B1 c.114-2A>G Pathogenic ★★ same condition
- AP4B1 p.Arg102Ter Pathogenic ★★ same condition
- AP4B1 p.Arg206Ter Pathogenic/Likely pathogenic ★★ same condition
- AP4B1 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same condition
- AP4B1 p.Arg393Ter Pathogenic ★★ same condition
- AP4B1 p.Arg406Ter Pathogenic/Likely pathogenic ★★ 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/ap4b1-p-pro80 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown