Is APOA5 p.Ser80Arg (c.240C>G) pathogenic?

APOA5 p.Ser80Arg (c.240C>G) is classified Likely benign in APOA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). AlphaMissense: likely benign (0.1093); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with APOA5 p.Ser80Arg (c.240C>G)?

APOA5 p.Ser80Arg (c.240C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is APOA5 p.Ser80Arg (c.240C>G) in the general population?

APOA5 p.Ser80Arg (c.240C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOA5 p.Ser80Arg (c.240C>G)?

AlphaMissense predicts likely benign (score 0.1093) — an in-silico prediction, not a clinical call.

APOA5 p.Ser80Arg

c.240C>G · VCV4843562

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1093 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1093	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -5.8
Regional constraint	o/e 0.92	unconstrained · MANE · 1,729 bp · p 0.086 · regional, not allelic
Overall
CADD	1.301	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APOA5
Protein: p.Ser80Arg
Coding: c.240C>G
MANE Select: NM_001371904
Type: single nucleotide variant
Location: chr11:116790989 (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.Ser80= Likely benign ★★ 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-ser80arg (accessed [today's date]).

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