AP4E1 p.Leu489=
c.1467C>G · VCV4924964
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.107%, eas)
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 0.35 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 5.439 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.107%
East Asian · 48/44,764 alleles
Filtering AF
0.0831%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0745%
Overall
0.0031%
50/1,613,024 alleles · rare
exomes 50/1,460,738 · genomes 0/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.107% | 933 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
| European (non-Finnish) | 8.48e-05% | 1,179,295 |
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
- AP4E1
- Protein
- p.Leu489=
- Coding
- c.1467C>G
- MANE Select
- NM_007347
- Type
- single nucleotide variant
- Location
- chr15:50950088 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42 · 4 PDB
Similar variants
- AP4E1 p.Arg1105Ter Pathogenic ★★ same type
- AP4E1 p.Arg304Ter Pathogenic/Likely pathogenic ★★ same type
- AP4E1 p.Ala119Ser Uncertain significance ★★ ⚠ same type
- AP4E1 p.Ala45Thr Uncertain significance ★★ ⚠ same type
- AP4E1 p.Ala475Val Uncertain significance ★★ ⚠ same type
- AP4E1 p.Ala65Val Uncertain significance ★★ ⚠ same type
- AP4E1 p.Ala678Val Uncertain significance ★★ ⚠ same type
- AP4E1 p.Arg304Gln 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/ap4e1-p-leu489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown