AP4E1 p.Leu487=
c.1459T>C · rs766895434 · VCV434238
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Conditions
1
Spastic paraplegia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.37 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -3.2, phastCons 0.96 |
| Overall | ||
| CADD | 6.516 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/60,010 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00143%
23/1,613,048 alleles · ultra-rare
exomes 13/1,460,796 · genomes 10/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,616 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,814 |
| African / African-American | 0.00133% | 74,922 |
| European (non-Finnish) | 0.000509% | 196,561 |
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.Leu487=
- Coding
- c.1459T>C
- MANE Select
- NM_007347
- dbSNP
- rs766895434
- Type
- single nucleotide variant
- Location
- chr15:50950080 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42 · 4 PDB
Similar variants
- AP4E1 p.Leu487Phe Uncertain significance ★★ ⚠ same residue
- AP4E1 p.Arg304Ter Pathogenic/Likely pathogenic ★★ same condition
- AP4E1 p.Ala119Ser Uncertain significance ★★ ⚠ same condition
- AP4E1 p.Ala45Thr Uncertain significance ★★ ⚠ same condition
- AP4E1 p.Ala475Val Uncertain significance ★★ ⚠ same condition
- AP4E1 p.Arg646Cys Uncertain significance ★★ same condition
- AP4E1 p.Asn1086Ser Uncertain significance ★★ ⚠ same condition
- AP4E1 p.Asp484Val 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/ap4e1-p-leu487 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown