APOE p.Asp128=
c.384C>T · rs766493265 · VCV2446926
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
Conditions
1
Cardiovascular phenotype
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 -5 | GERP -3.4 |
| Overall | ||
| CADD | 4.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 7/52,736 alleles
Filtering AF
0.0062%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00433%
Overall
0.00102%
16/1,569,948 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,534 |
| European (non-Finnish) | 0.000777% | 128,687 |
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
- APOE
- Protein
- p.Asp128=
- Coding
- c.384C>T
- MANE Select
- NM_000041
- dbSNP
- rs766493265
- Type
- single nucleotide variant
- Location
- chr19:44908680 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.13 · 31 PDB
- Residue 128
- the '8 x 22 aa approximate tandem repeats' region; an α-helix
Similar variants
- APOE p.Arg43Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- APOE p.Arg246Pro Uncertain significance ★★ same condition
- APOE p.Arg56His Uncertain significance ★★ ⚠ same condition
- APOE p.Gln119Pro Uncertain significance ★★ same condition
- APOE p.Gln181His Uncertain significance ★★ ⚠ same condition
- APOE p.Ser112Tyr Uncertain significance ★★ ⚠ same condition
- APOE p.Trp294Cys Uncertain significance ★★ ⚠ same condition
- APOE p.Val213Gly 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/apoe-p-asp128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown