Is APOB p.Pro4342= (c.13026A>G) pathogenic?

APOB p.Pro4342= (c.13026A>G) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-16). Very rare (popmax 0.00494%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Pro4342= (c.13026A>G)?

APOB p.Pro4342= (c.13026A>G) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Pro4342= (c.13026A>G) in the general population?

APOB p.Pro4342= (c.13026A>G) is very rare (popmax 0.00494%, nfe) (gnomAD).

APOB p.Pro4342=

c.13026A>G · rs188585568 · VCV920528

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00494%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.029	GERP -3.4
Overall
CADD	1.269	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00494% European (non-Finnish) · 58/1,173,556 alleles

Filtering AF 0.00388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00354%

Overall 0.00375% 60/1,601,320 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00494%	20,234
Remaining individualsnot grpmax-eligible	0.00162%	61,882
African / African-American	0.00135%	74,328

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.Pro4342=
Coding: c.13026A>G
MANE Select: NM_000384
dbSNP: rs188585568
Type: single nucleotide variant
Location: chr2:21002396 (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: familial hypercholesterolemia hypercholesterolemia, autosomal dominant, type B familial hypobetalipoproteinemia 1

Similar variants

APOB p.Pro4342Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
APOB c.1830-1G>A Pathogenic ★★ same condition
APOB c.2604+1G>A Likely pathogenic ★★ same condition
APOB c.537+1G>T Pathogenic/Likely pathogenic ★★ same condition
APOB p.Arg1333Ter Pathogenic ★★ same condition
APOB p.Arg2012Ter Pathogenic ★★ same condition
APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ same condition
APOB p.Arg2513Ter 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-pro4342 (accessed [today's date]).

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