Is APOE p.Arg231= (c.691C>A) pathogenic?

APOE p.Arg231= (c.691C>A) is classified Likely benign in APOE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-18). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with APOE p.Arg231= (c.691C>A)?

APOE p.Arg231= (c.691C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is APOE p.Arg231= (c.691C>A) in the general population?

APOE p.Arg231= (c.691C>A) is absent from gnomAD v4.1 (gnomAD).

APOE p.Arg231=

c.691C>A · rs1381171305 · VCV1756154

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,532,494)

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 1.5	GERP -0.6, phastCons 0.99
Overall
CADD	7.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,532,494). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APOE
Protein: p.Arg231=
Coding: c.691C>A
MANE Select: NM_000041
dbSNP: rs1381171305
Type: single nucleotide variant
Location: chr19:44908987 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 231: the '8 x 22 aa approximate tandem repeats' region; the 'lipid-binding and lipoprotein association' region; a binding site; a UniProt-annotated variant site (in hlpp3; apoe3 washington); an α-helix

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.Arg231Trp Uncertain significance ★ ⚠ same residue
APOE p.Arg231Leu Uncertain significance ★ ⚠ same residue
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

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-arg231 (accessed [today's date]).

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