Is APOA5 p.Pro272Arg (c.815C>G) pathogenic?

APOA5 p.Pro272Arg (c.815C>G) is classified Uncertain significance in APOA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely benign (0.0681); Absent from gnomAD v4.1.

How common is APOA5 p.Pro272Arg (c.815C>G) in the general population?

APOA5 p.Pro272Arg (c.815C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOA5 p.Pro272Arg (c.815C>G)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

APOA5 p.Pro272Arg

c.815C>G · VCV3687859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.34	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 -0.55	GERP -2.5
Regional constraint	o/e 0.92	unconstrained · MANE · 1,729 bp · p 0.086 · regional, not allelic
Overall
CADD	3.551	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Pro272Arg
Coding: c.815C>G
MANE Select: NM_001371904
Type: single nucleotide variant
Location: chr11:116790414 (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

Similar variants

APOA5 p.Pro272Gln Uncertain significance ★★ ⚠ same residue
APOA5 p.Pro272Leu Uncertain significance ★ ⚠ same residue
APOA5 p.Gln97Ter Pathogenic ★★ same type
APOA5 c.161+3G>A Uncertain significance ★★ same type
APOA5 c.161+5G>C Uncertain significance ★★ same type
APOA5 p.Ala105Ser Uncertain significance ★★ ⚠ same type
APOA5 p.Ala244Ser Uncertain significance ★★ ⚠ same type
APOA5 p.Ala302Val Uncertain significance ★★ ⚠ same type

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-pro272arg (accessed [today's date]).

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