Is APOA5 p.Asp37fs (c.111del) pathogenic?

APOA5 p.Asp37fs (c.111del) is classified Conflicting classifications of pathogenicity in APOA5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-06-21). Very rare (popmax 0.00168%, amr); Associated with Cardiovascular phenotype.

What condition is associated with APOA5 p.Asp37fs (c.111del)?

APOA5 p.Asp37fs (c.111del) is associated with Cardiovascular phenotype (ClinVar).

How common is APOA5 p.Asp37fs (c.111del) in the general population?

APOA5 p.Asp37fs (c.111del) is very rare (popmax 0.00168%, amr) (gnomAD).

APOA5 p.Asp37fs

c.111del · rs1365337213 · VCV1428390

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (2 of 3, 50 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 3.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,642 alleles

Overall 0.000137% 2/1,457,964 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,642
African / African-American	0.00133%	74,972

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.Asp37fs
Coding: c.111del
MANE Select: NM_001371904
dbSNP: rs1365337213
Type: Deletion
Location: chr11:116791636 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.38
Residue 37: a UniProt-annotated variant site (in)

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.Asp37Glu Benign/Likely benign ★★ same residue
APOA5 p.Pro318fs Likely pathogenic ★ same condition
APOA5 p.His182fs Conflicting classifications of pathogenicity ★ same condition
APOA5 p.Ile296fs Conflicting classifications of pathogenicity ★ same condition
APOA5 p.Leu242fs Conflicting classifications of pathogenicity ★ same condition
APOA5 p.Pro193_Gly201delinsArg Uncertain significance ★ same condition
APOA5 p.Thr266fs Conflicting classifications of pathogenicity ★ same condition
APOA5 p.Asp332fs Pathogenic/Likely pathogenic ★★ 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-asp37fs (accessed [today's date]).

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