APOE p.Glu197=
c.591G>A · rs928986800 · VCV1750497
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000355%, nfe)
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 6.8 | GERP -0.67, phastCons 1 |
| Overall | ||
| CADD | 9.741 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000355%
European (non-Finnish) · 4/1,125,220 alleles
Filtering AF
8.3e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.6e-05%
Overall
0.0003%
4/1,332,762 alleles · very rare
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.Glu197=
- Coding
- c.591G>A
- MANE Select
- NM_000041
- dbSNP
- rs928986800
- Type
- single nucleotide variant
- Location
- chr19:44908887 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.13 · 31 PDB
- Residue 197
- 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-glu197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown