AP4B1 p.Glu504=
c.1512G>A · rs1553257180 · VCV515053
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.59 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.51 | gain · loss 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 0.35, phastCons 1 |
| Overall | ||
| CADD | 19.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000494%
Overall
0.000274%
4/1,461,892 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| African / African-American | 0.004% | 25,010 |
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.Glu504=
- Coding
- c.1512G>A
- MANE Select
- NM_001253852
- dbSNP
- rs1553257180
- Type
- single nucleotide variant
- Location
- chr1:113896037 (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 c.114-2A>C Pathogenic ★★ same type
- AP4B1 c.114-2A>G Pathogenic ★★ same type
- AP4B1 p.Arg102Ter Pathogenic ★★ same type
- AP4B1 p.Arg206Ter Pathogenic/Likely pathogenic ★★ same type
- AP4B1 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same type
- AP4B1 p.Arg393Ter Pathogenic ★★ same type
- AP4B1 p.Arg406Ter Pathogenic/Likely pathogenic ★★ same type
- AP4B1 p.Arg514Ter 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/ap4b1-p-glu504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown