AP4E1 p.Ser819=
c.2457T>C · VCV4924978
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
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 Δ0.58 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 9.408 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,179,878 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,613,718 alleles · very rare
exomes 5/1,461,500 · genomes 1/152,218 · 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.Ser819=
- Coding
- c.2457T>C
- MANE Select
- NM_007347
- Type
- single nucleotide variant
- Location
- chr15:50997436 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42 · 4 PDB
- Residue 819
- the 'interaction with tepsin' region
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-ser819 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown