Is APOE p.Pro285= (c.855C>G) pathogenic?

APOE p.Pro285= (c.855C>G) is classified Likely benign in APOE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-24). Very rare (popmax 0.000679%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOE p.Pro285= (c.855C>G)?

APOE p.Pro285= (c.855C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is APOE p.Pro285= (c.855C>G) in the general population?

APOE p.Pro285= (c.855C>G) is very rare (popmax 0.000679%, nfe) (gnomAD).

APOE p.Pro285=

c.855C>G · VCV3934752

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000679%, nfe)

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 -0.75	GERP -3.1
Overall
CADD	6.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000679% European (non-Finnish) · 8/1,178,946 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000499% 8/1,601,614 alleles · very rare exomes 8/1,449,270 · genomes 0/152,344 · joint denominator

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.Pro285=
Coding: c.855C>G
MANE Select: NM_000041
Type: single nucleotide variant
Location: chr19:44909151 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 285: the 'lipid-binding and lipoprotein association' region; the 'homooligomerization' region; the 'specificity for association with vldl' region; a UniProt-annotated variant site (in hlpp3; apoe3 washington)

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.Pro285His 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
APOE p.Trp294Cys 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-pro285 (accessed [today's date]).

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