Is APOA5 p.Val199= (c.597G>A) pathogenic?

APOA5 p.Val199= (c.597G>A) is classified Likely benign in APOA5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). Ultra-rare (popmax 0.017%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOA5 p.Val199= (c.597G>A)?

APOA5 p.Val199= (c.597G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is APOA5 p.Val199= (c.597G>A) in the general population?

APOA5 p.Val199= (c.597G>A) is ultra-rare (popmax 0.017%, nfe) (gnomAD).

APOA5 p.Val199=

c.597G>A · rs374702553 · VCV1750829

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, nfe)

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 -0.093	GERP 1.1
Overall
CADD	8.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% European (non-Finnish) · 200/1,179,846 alleles

Filtering AF 0.015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.0132% 212/1,610,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.017%	5,899
Remaining individualsnot grpmax-eligible	0.0144%	6,937
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,574
African / African-American	0.00267%	37,471

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.Val199=
Coding: c.597G>A
MANE Select: NM_001371904
dbSNP: rs374702553
Type: single nucleotide variant
Location: chr11:116790632 (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.Val199Met 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-val199 (accessed [today's date]).

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