Is APOE p.Ala184= (c.552C>T) pathogenic?

APOE p.Ala184= (c.552C>T) is classified Likely benign in APOE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-06). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with APOE p.Ala184= (c.552C>T)?

APOE p.Ala184= (c.552C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is APOE p.Ala184= (c.552C>T) in the general population?

APOE p.Ala184= (c.552C>T) is absent from gnomAD v4.1 (gnomAD).

APOE p.Ala184=

c.552C>T · rs1599953921 · VCV1748127

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 -0.089	GERP -3.4
Overall
CADD	7.273	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APOE
Protein: p.Ala184=
Coding: c.552C>T
MANE Select: NM_000041
dbSNP: rs1599953921
Type: single nucleotide variant
Location: chr19:44908848 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 184: the '8 x 22 aa approximate tandem repeats' region

Full APOE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ala184 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown