Is APOB p.His3410fs (c.10230_10234del) pathogenic?

APOB p.His3410fs (c.1023010234del) is classified Pathogenic in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-21). Very rare (popmax 8.47e-05%, nfe); Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.His3410fs (c.10230_10234del)?

APOB p.His3410fs (c.10230_10234del) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.His3410fs (c.10230_10234del) in the general population?

APOB p.His3410fs (c.10230_10234del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

APOB p.His3410fs

c.10230_10234del · rs1663149096 · VCV2922354

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 26 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 0.83, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,972 alleles

Overall 0.000657% 1/152,186 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APOB
Protein: p.His3410fs
Coding: c.10230_10234del
MANE Select: NM_000384
dbSNP: rs1663149096
Type: Deletion
Location: chr2:21006634 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3410: the 'heparin-binding' region

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

Also linked: familial hypobetalipoproteinemia 1

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-his3410fs (accessed [today's date]).

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