Is APOC2 p.Glu100= (c.300G>A) pathogenic?

APOC2 p.Glu100= (c.300G>A) is classified Likely benign in APOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-17). Very rare (popmax 0.000339%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOC2 p.Glu100= (c.300G>A)?

APOC2 p.Glu100= (c.300G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is APOC2 p.Glu100= (c.300G>A) in the general population?

APOC2 p.Glu100= (c.300G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

APOC2 p.Glu100=

c.300G>A · rs1001285509 · VCV2447636

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, 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 -7.4	GERP -3.9
Overall
CADD	0.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,726 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,144 alleles · very rare

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: APOC2
Protein: p.Glu100=
Coding: c.300G>A
MANE Select: NM_000483
dbSNP: rs1001285509
Type: single nucleotide variant
Location: chr19:44949243 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 4 PDB
Residue 100: the 'lipoprotein lipase cofactor' region

Full APOC2 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

APOC2 p.Glu100Lys Uncertain significance ★ ⚠ same residue
APOC2 p.Gln25Ter Likely pathogenic ★★ same condition
APOC2 p.Ala54Asp Uncertain significance ★★ ⚠ same condition
APOC2 p.Ala55Thr Uncertain significance ★★ ⚠ same condition
APOC2 p.Ser76Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr23Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr86Arg Uncertain significance ★★ ⚠ same condition
APOC2 p.Val67Ile 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/apoc2-p-glu100 (accessed [today's date]).

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