AP4E1 p.Thr562=
c.1686A>C · rs375848961 · VCV1343986
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, afr)
Conditions
2
Spastic paraplegia
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 0.08 | GERP 0.1 |
| Overall | ||
| CADD | 2.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
African / African-American · 18/75,064 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.00112%
18/1,614,198 alleles · ultra-rare
exomes 10/1,461,836 · genomes 8/152,362 · joint denominator
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.Thr562=
- Coding
- c.1686A>C
- MANE Select
- NM_007347
- dbSNP
- rs375848961
- Type
- single nucleotide variant
- Location
- chr15:50958629 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42 · 4 PDB
Similar variants
- 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.Asn311Ser 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-thr562 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown