Is APOA5 p.Ala325= (c.975C>T) pathogenic?

APOA5 p.Ala325= (c.975C>T) is classified Benign/Likely benign in APOA5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.22%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOA5 p.Ala325= (c.975C>T)?

APOA5 p.Ala325= (c.975C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is APOA5 p.Ala325= (c.975C>T) in the general population?

APOA5 p.Ala325= (c.975C>T) is low-frequency (popmax 1.22%, afr) (gnomAD).

APOA5 p.Ala325=

c.975C>T · rs137942813 · VCV496501

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, 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 0.35	GERP 0.16, phastCons 0.2
Overall
CADD	1.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.22% African / African-American · 912/75,060 alleles

Filtering AF 1.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.0626% 1,011/1,614,254 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.22%	82
Remaining individualsnot grpmax-eligible	0.08%	1,250
Admixed American	0.0533%	1,876
Middle Eastern	0.0495%	2,021
South Asian	0.00659%	15,182
European (non-Finnish)	0.000678%	147,506

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.Ala325=
Coding: c.975C>T
MANE Select: NM_001371904
dbSNP: rs137942813
Type: single nucleotide variant
Location: chr11:116790254 (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

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

Similar variants

APOA5 p.Ala325Ser Uncertain significance ★ ⚠ same residue
APOA5 p.Ala325Thr Uncertain significance ★ ⚠ same residue
APOA5 c.161+3G>A Uncertain significance ★★ same condition
APOA5 c.161+5G>C Uncertain significance ★★ same condition
APOA5 p.Ala244Ser Uncertain significance ★★ ⚠ same condition
APOA5 p.Ala302Val Uncertain significance ★★ ⚠ same condition
APOA5 p.Ala82Val Uncertain significance ★★ ⚠ same condition
APOA5 p.Arg226Cys 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/apoa5-p-ala325 (accessed [today's date]).

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