Is APOA5 p.Pro318= (c.954A>C) pathogenic?

APOA5 p.Pro318= (c.954A>C) is classified Likely benign in APOA5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-12). Very rare (popmax 0.00833%, amr); Associated with Cardiovascular phenotype.

What condition is associated with APOA5 p.Pro318= (c.954A>C)?

APOA5 p.Pro318= (c.954A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is APOA5 p.Pro318= (c.954A>C) in the general population?

APOA5 p.Pro318= (c.954A>C) is very rare (popmax 0.00833%, amr) (gnomAD).

APOA5 p.Pro318=

c.954A>C · rs939491246 · VCV2961422

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, 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 -20	GERP -6.6
Overall
CADD	0.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,012 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000434% 7/1,614,150 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	8.47e-05%	1,180,054

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.Pro318=
Coding: c.954A>C
MANE Select: NM_001371904
dbSNP: rs939491246
Type: single nucleotide variant
Location: chr11:116790275 (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.Pro318fs Likely pathogenic ★ 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
APOA5 p.Arg233Gln 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-pro318 (accessed [today's date]).

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