AP4E1 p.Thr698=
c.2094A>G · rs1419630030 · VCV714654
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 3.4 | GERP -0.83, phastCons 1 |
| Overall | ||
| CADD | 8.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,928 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,613,774 alleles · very rare
exomes 2/1,461,556 · genomes 1/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,928 |
| European (non-Finnish) | 0.00017% | 589,953 |
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.Thr698=
- Coding
- c.2094A>G
- MANE Select
- NM_007347
- dbSNP
- rs1419630030
- Type
- single nucleotide variant
- Location
- chr15:50993373 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.42 · 4 PDB
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-thr698 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown