Is APOA5 p.Ser232= (c.696C>A) pathogenic?

APOA5 p.Ser232= (c.696C>A) is classified Likely benign in APOA5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-19). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with APOA5 p.Ser232= (c.696C>A)?

APOA5 p.Ser232= (c.696C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is APOA5 p.Ser232= (c.696C>A) in the general population?

APOA5 p.Ser232= (c.696C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

APOA5 p.Ser232=

c.696C>A · rs146781249 · VCV1756359

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -6.4	GERP -5.9
Overall
CADD	1.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.00376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00338%

Overall 0.00469% 75/1,598,800 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.0129%	7,772
Admixed American	0.00835%	11,975
South Asian	0.0055%	18,195
European (non-Finnish)	0.00476%	21,021

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.Ser232=
Coding: c.696C>A
MANE Select: NM_001371904
dbSNP: rs146781249
Type: single nucleotide variant
Location: chr11:116790533 (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.Ser232Pro 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
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-ser232 (accessed [today's date]).

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