AP4E1 p.Val969=
c.2907G>A · rs778511777 · VCV1610465
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00178%, nfe)
Conditions
1
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 0.55 | GERP 0.74, phastCons 0.99 |
| Overall | ||
| CADD | 12.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
European (non-Finnish) · 21/1,179,930 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.0013%
21/1,613,826 alleles · very rare
exomes 20/1,461,648 · genomes 1/152,178 · 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.Val969=
- Coding
- c.2907G>A
- MANE Select
- NM_007347
- dbSNP
- rs778511777
- Type
- single nucleotide variant
- Location
- chr15:50999074 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42 · 4 PDB
- Residue 969
- the 'interaction with tepsin' region
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.Asp484Val Uncertain significance ★★ ⚠ same condition
- AP4E1 p.Asp938Gly 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-val969 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown