Is APOA1 p.Pro189fs (c.551_564dup) pathogenic?

APOA1 p.Pro189fs (c.551564dup) is classified Uncertain significance in APOA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). Absent from gnomAD.

How common is APOA1 p.Pro189fs (c.551_564dup) in the general population?

APOA1 p.Pro189fs (c.551_564dup) is absent from gnomAD (gnomAD).

APOA1 p.Pro189fs

c.551_564dup · rs2540288749 · VCV2809567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.4	GERP 3.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APOA1
Protein: p.Pro189fs
Coding: c.551_564dup
MANE Select: NM_000039
dbSNP: rs2540288749
Type: Duplication
Location: chr11:116836047 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 31 PDB
Residue 189: the '10 x approximate tandem repeats' region; a UniProt-annotated variant site (in fha2; no protein expression); a UniProt-annotated variant site (in hdl deficiency; with periorbital xanthelasmas; decreased protein abundance); a UniProt-annotated variant site (in fha2; missing protein expression); a UniProt-annotated variant site (in); an α-helix

Full APOA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOA1 p.Pro189Arg Uncertain significance ★ ⚠ same residue
APOA1 p.Pro189= Likely benign ★ same residue
APOA1 p.Asn265_Thr266insAsn Uncertain significance ★★ same type
APOA1 p.Gln29fs Conflicting classifications of pathogenicity ★ same type
APOA1 p.His186fs Uncertain significance ★ same type
APOA1 p.Leu198Ter Uncertain significance ★ same type
APOA1 p.Ala178_His179insArgAlaArgAla 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/apoa1-p-pro189fs (accessed [today's date]).

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