Is APOB p.Glu1483= (c.4449A>G) pathogenic?

APOB p.Glu1483= (c.4449A>G) is classified Conflicting classifications of pathogenicity in APOB (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-04-01). Low-frequency (popmax 1.2%, sas); Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Glu1483= (c.4449A>G)?

APOB p.Glu1483= (c.4449A>G) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypercholesterolemia, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Glu1483= (c.4449A>G) in the general population?

APOB p.Glu1483= (c.4449A>G) is low-frequency (popmax 1.2%, sas) (gnomAD).

APOB p.Glu1483=

c.4449A>G · rs151018874 · VCV334142

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, sas)

Conditions

hypercholesterolemia, autosomal dominant, type B

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 -0.28	GERP -0.79
Overall
CADD	5.748	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.2% South Asian · 1,094/91,084 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.0914% 1,475/1,614,216 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.2%	83
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.0317%	3,159
European (non-Finnish)	0.0246%	4,069
East Asian	0.00446%	22,438
African / African-American	0.004%	25,019
Finnishnot grpmax-eligible	0.00312%	32,023

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.Glu1483=
Coding: c.4449A>G
MANE Select: NM_000384
dbSNP: rs151018874
Type: single nucleotide variant
Location: chr2:21012419 (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

hypercholesterolemia, autosomal dominant, type B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia familial hypobetalipoproteinemia 1

Similar variants

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
APOB p.Arg2520Ter 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-glu1483 (accessed [today's date]).

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