Is APOE p.Phe283= (c.849C>T) pathogenic?

APOE p.Phe283= (c.849C>T) is classified Likely benign in APOE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-25). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOE p.Phe283= (c.849C>T)?

APOE p.Phe283= (c.849C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is APOE p.Phe283= (c.849C>T) in the general population?

APOE p.Phe283= (c.849C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

APOE p.Phe283=

c.849C>T · rs954301448 · VCV1763601

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 0.026	GERP -0.69, phastCons 0.86
Overall
CADD	12.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,860 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.00144% 23/1,601,222 alleles · very rare exomes 21/1,449,050 · genomes 2/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,430
European (non-Finnish)	0.0017%	58,936
Remaining individualsnot grpmax-eligible	0.00161%	62,186

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.Phe283=
Coding: c.849C>T
MANE Select: NM_000041
dbSNP: rs954301448
Type: single nucleotide variant
Location: chr19:44909145 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 283: 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); 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.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-phe283 (accessed [today's date]).

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