Is APOB p.Ile4377fs (c.13129_13130del) pathogenic?

APOB p.Ile4377fs (c.1312913130del) is classified Pathogenic in APOB (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with hypercholesterolemia, familial, 1.

What condition is associated with APOB p.Ile4377fs (c.13129_13130del)?

APOB p.Ile4377fs (c.13129_13130del) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is APOB p.Ile4377fs (c.13129_13130del) in the general population?

APOB p.Ile4377fs (c.13129_13130del) is absent from gnomAD (gnomAD).

APOB p.Ile4377fs

c.13129_13130del · rs1553382325 · VCV440510

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypercholesterolemia, familial, 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	escapes	premature termination codon in the last exon (29 of 29) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.21	GERP -0.41

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: APOB
Protein: p.Ile4377fs
Coding: c.13129_13130del
MANE Select: NM_000384
dbSNP: rs1553382325
Type: Deletion
Location: chr2:21002292 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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

Disease context

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

Similar variants

APOB c.12088-13del Benign ★★ same condition
APOB p.Asn1531fs Pathogenic ★ same condition
APOB p.Gln2383fs Likely pathogenic ★ same condition
APOB p.Glu1004fs Pathogenic ★ same condition
APOB p.Glu4387fs Pathogenic ★ same condition
APOB p.Leu14fs Pathogenic ★ same condition
APOB p.Thr170fs Likely pathogenic ★ same condition
APOB p.Ala13_Leu14del 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/apob-p-ile4377fs (accessed [today's date]).

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