Is APOB p.Ala594fs (c.1780del) pathogenic?

APOB p.Ala594fs (c.1780del) is classified Likely pathogenic in APOB (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Ala594fs (c.1780del)?

APOB p.Ala594fs (c.1780del) is associated with hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Ala594fs (c.1780del) in the general population?

APOB p.Ala594fs (c.1780del) is absent from gnomAD (gnomAD).

APOB p.Ala594fs

c.1780del · rs2465421714 · VCV1895395

Likely pathogenic Single submitter

Classification

Likely 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	predicted	premature termination codon in exon 13 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, 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: APOB
Protein: p.Ala594fs
Coding: c.1780del
MANE Select: NM_000384
dbSNP: rs2465421714
Type: Deletion
Location: chr2:21028376 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 594: the vitellogenin domain

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 c.226_237+1del Pathogenic/Likely pathogenic ★★ same condition
APOB c.78_82+5del Likely pathogenic ★★ same condition
APOB p.Asn1755fs Pathogenic ★★ same condition
APOB p.Asn1772fs Pathogenic/Likely pathogenic ★★ same condition
APOB p.Gly3617fs Pathogenic/Likely pathogenic ★★ same condition
APOB p.His2227fs Pathogenic ★★ same condition
APOB p.Leu1345fs Pathogenic ★★ same condition
APOB p.Leu2914fs Pathogenic/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-ala594fs (accessed [today's date]).

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