Is APOA5 p.Gln97Ter (c.289C>T) pathogenic?

APOA5 p.Gln97Ter (c.289C>T) is classified Pathogenic in APOA5 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0217%, nfe); Associated with hypertriglyceridemia.

What condition is associated with APOA5 p.Gln97Ter (c.289C>T)?

APOA5 p.Gln97Ter (c.289C>T) is associated with hypertriglyceridemia, hyperlipoproteinemia type V, hypertriglyceridemia 1 (ClinVar).

How common is APOA5 p.Gln97Ter (c.289C>T) in the general population?

APOA5 p.Gln97Ter (c.289C>T) is ultra-rare (popmax 0.0217%, nfe) (gnomAD).

APOA5 p.Gln97Ter

c.289C>T · rs201079485 · VCV381733

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, nfe)

Conditions

hypertriglyceridemia

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 (3 of 3) — 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 7.4	GERP 3.1, phastCons 1
Overall
CADD	36.0	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 0.0217% European (non-Finnish) · 256/1,180,024 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.0171% 276/1,613,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0217%	4,609
Finnishnot grpmax-eligible	0.019%	5,259
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.004%	24,981
Admixed American	0.00333%	30,006

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: APOA5
Protein: p.Gln97Ter
Coding: c.289C>T
MANE Select: NM_001371904
dbSNP: rs201079485
Type: single nucleotide variant
Location: chr11:116790940 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.38

Full APOA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypertriglyceridemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperlipoproteinemia type V hypertriglyceridemia 1 hyperlipoproteinemia

Similar variants

APOA5 p.Pro193Leu Uncertain significance ★★ ⚠ same condition
APOA5 c.*158C>T Benign ★★ same condition
APOA5 p.Ser19Trp Benign/Likely benign ★★ ⚠ same condition
APOA5 p.Arg223Cys Likely pathogenic ★ ⚠ same condition
APOA5 p.Cys227Ter Likely pathogenic ★ same condition
APOA5 p.Arg343Cys Uncertain significance ★ ⚠ same condition
APOA5 p.Gln275Ter Conflicting classifications of pathogenicity ★ same condition
APOA5 p.Gly185Cys Conflicting classifications of pathogenicity ★ ⚠ 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/apoa5-p-gln97ter (accessed [today's date]).

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