Is APOC2 p.Gln92Ter (c.274C>T) pathogenic?

APOC2 p.Gln92Ter (c.274C>T) is classified Pathogenic/Likely pathogenic in APOC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-06). Very rare (popmax 0.00133%, afr); Associated with familial apolipoprotein C-II deficiency.

What condition is associated with APOC2 p.Gln92Ter (c.274C>T)?

APOC2 p.Gln92Ter (c.274C>T) is associated with familial apolipoprotein C-II deficiency (ClinVar).

How common is APOC2 p.Gln92Ter (c.274C>T) in the general population?

APOC2 p.Gln92Ter (c.274C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

APOC2 p.Gln92Ter

c.274C>T · rs199563828 · VCV1685529

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

familial apolipoprotein C-II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,910 alleles

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

Overall 0.00031% 5/1,613,880 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,910
European (non-Finnish)	0.000339%	294,997

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.Gln92Ter
Coding: c.274C>T
MANE Select: NM_000483
dbSNP: rs199563828
Type: single nucleotide variant
Location: chr19:44949217 (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 92: an α-helix; the 'lipoprotein lipase cofactor' region

Full APOC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial apolipoprotein C-II deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOC2 p.Ala54Asp Uncertain significance ★★ ⚠ same condition
APOC2 p.Ala55Thr Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr23Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr86Arg Uncertain significance ★★ ⚠ same condition
APOC2 c.56-4G>C Benign ★★ same condition
APOC2 p.Glu60Lys Benign/Likely benign ★★ same condition
APOC2 c.216-1G>A Pathogenic ★ same condition
APOC2 p.Met1Val Likely pathogenic ★ 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-gln92ter (accessed [today's date]).

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