Is APOB p.Leu9fs (c.26_33del) pathogenic?

APOB p.Leu9fs (c.2633del) is classified Benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-28). Very rare (popmax 0.000191%, nfe).

How common is APOB p.Leu9fs (c.26_33del) in the general population?

APOB p.Leu9fs (c.26_33del) is very rare (popmax 0.000191%, nfe) (gnomAD).

APOB p.Leu9fs

c.26_33del · rs1060499842 · VCV402371

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000191%, nfe)

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 1 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 0.6, phastCons 0.2
Region caveats
Repeat context	tandem	(GCAGCAGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000191% European (non-Finnish) · 2/1,047,522 alleles

Filtering AF 3.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000238% 3/1,257,884 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0019%	52,558
European (non-Finnish)grpmax	0.000191%	523,760

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu9fs
Coding: c.26_33del
MANE Select: NM_000384
dbSNP: rs1060499842
Type: Deletion
Location: chr2:21043913 (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

Similar variants

APOB p.Leu9dup Uncertain significance ★★ same residue
APOB c.226_237+1del Pathogenic/Likely pathogenic ★★ same type
APOB c.78_82+5del Likely pathogenic ★★ same type
APOB p.Asn1755fs Pathogenic ★★ same type
APOB p.Asn1772fs Pathogenic/Likely pathogenic ★★ same type
APOB p.Gly3617fs Pathogenic/Likely pathogenic ★★ same type
APOB p.His2227fs Pathogenic ★★ same type
APOB p.Leu1345fs Pathogenic ★★ same type

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-leu9fs (accessed [today's date]).

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