Is APOA5 p.Arg143fs (c.427del) pathogenic?

APOA5 p.Arg143fs (c.427del) is classified Conflicting classifications of pathogenicity in APOA5 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-04-16). Ultra-rare (popmax 0.0165%, sas); Associated with hyperlipoproteinemia type V.

What condition is associated with APOA5 p.Arg143fs (c.427del)?

APOA5 p.Arg143fs (c.427del) is associated with hyperlipoproteinemia type V (ClinVar).

How common is APOA5 p.Arg143fs (c.427del) in the general population?

APOA5 p.Arg143fs (c.427del) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

APOA5 p.Arg143fs

c.427del · rs777046568 · VCV1678148

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Conditions

hyperlipoproteinemia type V

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 in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.23	GERP -1.5, phastCons 0.006
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,090 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00223% 36/1,613,662 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,073
Admixed American	0.00167%	60,014
European (non-Finnish)	0.00161%	62,107
African / African-American	0.00133%	74,948

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.Arg143fs
Coding: c.427del
MANE Select: NM_001371904
dbSNP: rs777046568
Type: Deletion
Location: chr11:116790802 (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

hyperlipoproteinemia type V — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOA5 p.Arg143His Uncertain significance ★★ ⚠ same residue
APOA5 p.Arg143= Likely benign ★★ same residue
APOA5 p.Arg40fs Likely pathogenic ★ same condition
APOA5 p.Tyr194fs Pathogenic ★ same condition
APOA5 p.Arg143Ser Uncertain significance ★ ⚠ same residue
APOA5 p.Asp332fs Pathogenic/Likely pathogenic ★★ same condition
APOA5 p.Gln97Ter Pathogenic ★★ same condition
APOA5 p.Pro193Leu 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-arg143fs (accessed [today's date]).

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