APOE p.Pro28=
c.84G>A · rs150688032 · VCV3231977
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, 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 -0.86 | GERP -2.1 |
| Overall | ||
| CADD | 7.128 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,970 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00217%
35/1,613,498 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,993 |
| South Asian | 0.00439% | 22,763 |
| East Asian | 0.00223% | 44,876 |
| European (non-Finnish) | 0.00212% | 47,198 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,454 |
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.Pro28=
- Coding
- c.84G>A
- MANE Select
- NM_000041
- dbSNP
- rs150688032
- Type
- single nucleotide variant
- Location
- chr19:44907800 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.13 · 31 PDB
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-pro28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown