Is APOB p.Pro3Gln (c.8_9delinsAA) pathogenic?

APOB p.Pro3Gln (c.89delinsAA) is classified Uncertain significance in APOB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-11). No gnomAD frequency available for this variant; Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Pro3Gln (c.8_9delinsAA)?

APOB p.Pro3Gln (c.8_9delinsAA) is associated with Cardiovascular phenotype, hypercholesterolemia, autosomal dominant, type B, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Pro3Gln (c.8_9delinsAA) in the general population?

APOB p.Pro3Gln (c.8_9delinsAA) is no gnomAD frequency available for this variant (gnomAD).

APOB p.Pro3Gln

c.8_9delinsAA · rs2465464345 · VCV3231459

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -1.5
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.91 · regional, not allelic

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.Pro3Gln
Coding: c.8_9delinsAA
MANE Select: NM_000384
dbSNP: rs2465464345
Type: Indel
Location: chr2:21043937 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypercholesterolemia, autosomal dominant, type B familial hypobetalipoproteinemia 1

Similar variants

APOB p.Pro3Arg Uncertain significance ★ ⚠ same residue
APOB p.Pro3Leu Uncertain significance ★ ⚠ same residue
APOB p.Pro3= Likely benign ★ same residue
APOB p.Ala4148Glu Uncertain significance ★★ same condition
APOB p.Leu12_Ala16delinsProAlaLeu Uncertain significance ★★ same condition
APOB p.Phe3687Ter Pathogenic ★ same condition
APOB c.4217-15_4217-14delinsAT Uncertain significance ★ same condition
APOB p.9_11LAL[1] Conflicting classifications of pathogenicity ★ 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-pro3gln (accessed [today's date]).

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