Is APOB p.Ser4267fs (c.12797dup) pathogenic?

APOB p.Ser4267fs (c.12797dup) is classified Pathogenic in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-25). Absent from gnomAD; Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Ser4267fs (c.12797dup)?

APOB p.Ser4267fs (c.12797dup) is associated with hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Ser4267fs (c.12797dup) in the general population?

APOB p.Ser4267fs (c.12797dup) is absent from gnomAD (gnomAD).

APOB p.Ser4267fs

c.12797dup · rs769836306 · VCV3236789

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypercholesterolemia, autosomal dominant, type B

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 0.82	GERP -3.2, phastCons 0.001

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.Ser4267fs
Coding: c.12797dup
MANE Select: NM_000384
dbSNP: rs769836306
Type: Duplication
Location: chr2:21002624 (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, autosomal dominant, type B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOB p.Ser4267Leu Likely benign ★ same residue
APOB p.Asn3211fs Pathogenic ★★ same condition
APOB p.Tyr4380Ter Uncertain significance ★★ same condition
APOB c.12088-23dup Benign/Likely benign ★★ same condition
APOB p.Arg3391fs Pathogenic ★ same condition
APOB p.Asn2865fs Pathogenic ★ same condition
APOB p.Ile4194fs Likely pathogenic ★ same condition
APOB p.Lys1982fs 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/apob-p-ser4267fs (accessed [today's date]).

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