AP4E1 p.Tyr86=
c.258T>C · rs143624283 · VCV210202
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0777%, nfe)
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 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 8.782 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0777%
European (non-Finnish) · 917/1,179,618 alleles
Filtering AF
0.0735%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0719%
Overall
0.0621%
1,002/1,613,502 alleles · ultra-rare
exomes 939/1,461,162 · genomes 63/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0777% | 1,286 |
| Remaining individualsnot grpmax-eligible | 0.0656% | 1,524 |
| Admixed American | 0.05% | 2,001 |
| African / African-American | 0.012% | 8,339 |
| East Asian | 0.0112% | 8,947 |
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.Tyr86=
- Coding
- c.258T>C
- MANE Select
- NM_007347
- dbSNP
- rs143624283
- Type
- single nucleotide variant
- Location
- chr15:50915483 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42 · 4 PDB
Similar variants
- AP4E1 p.Tyr86Cys 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-tyr86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown