Is APOB p.Arg3391fs (c.10171dup) pathogenic?

APOB p.Arg3391fs (c.10171dup) is classified Pathogenic in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-22). Associated with familial hypobetalipoproteinemia 1.

What condition is associated with APOB p.Arg3391fs (c.10171dup)?

APOB p.Arg3391fs (c.10171dup) is associated with familial hypobetalipoproteinemia 1, hypercholesterolemia, autosomal dominant, type B (ClinVar).

APOB p.Arg3391fs

c.10171dup · VCV4785641

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

familial hypobetalipoproteinemia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 26 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: APOB
Protein: p.Arg3391fs
Coding: c.10171dup
MANE Select: NM_000384
Type: Duplication
Location: chr2:21006696 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3391: the 'ldl receptor binding' region; the 'heparin-binding' region; the 'basic (possible receptor binding region)' region

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

Disease context

familial hypobetalipoproteinemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypercholesterolemia, autosomal dominant, type B

Similar variants

APOB p.Asn3211fs Pathogenic ★★ same condition
APOB p.Tyr4380Ter Uncertain significance ★★ same condition
APOB c.12088-23dup Benign/Likely benign ★★ same condition
APOB p.Asn2865fs Pathogenic ★ same condition
APOB p.Ile4194fs Likely pathogenic ★ same condition
APOB p.Lys1982fs Likely pathogenic ★ same condition
APOB p.Phe2845fs Pathogenic ★ same condition
APOB p.Pro3061fs 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/apob-p-arg3391fs (accessed [today's date]).

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