Is APOE p.Ser314= (c.942C>T) pathogenic?

APOE p.Ser314= (c.942C>T) is classified Likely benign in APOE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-03-01). Ultra-rare (popmax 0.0251%, amr); Associated with Cardiovascular phenotype.

What condition is associated with APOE p.Ser314= (c.942C>T)?

APOE p.Ser314= (c.942C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is APOE p.Ser314= (c.942C>T) in the general population?

APOE p.Ser314= (c.942C>T) is ultra-rare (popmax 0.0251%, amr) (gnomAD).

APOE p.Ser314=

c.942C>T · rs1051068315 · VCV726778

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0251%, amr)

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 -2.8	GERP -3.2
Overall
CADD	3.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0251% Admixed American · 15/59,880 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.00188% 30/1,596,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0251%	3,992
Remaining individualsnot grpmax-eligible	0.00161%	62,104
European (non-Finnish)	0.00119%	84,231

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.Ser314=
Coding: c.942C>T
MANE Select: NM_000041
dbSNP: rs1051068315
Type: single nucleotide variant
Location: chr19:44909238 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 314: the 'homooligomerization' region; a UniProt-annotated variant site (in hlpp3; apoe3 washington); a UniProt-annotated variant site (in apoe4 hg)

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.Ser314Arg Conflicting classifications of pathogenicity ★ ⚠ 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-ser314 (accessed [today's date]).

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