Is APOB p.Ala4483= (c.13449G>A) pathogenic?

APOB p.Ala4483= (c.13449G>A) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-07). Rare (popmax 0.269%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Ala4483= (c.13449G>A)?

APOB p.Ala4483= (c.13449G>A) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Ala4483= (c.13449G>A) in the general population?

APOB p.Ala4483= (c.13449G>A) is rare (popmax 0.269%, afr) (gnomAD).

APOB p.Ala4483=

c.13449G>A · rs138421941 · VCV544108

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.269%, afr)

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 -0.84	GERP -3.4
Overall
CADD	1.277	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.269% African / African-American · 202/75,014 alleles

Filtering AF 0.239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.227%

Overall 0.0153% 247/1,613,954 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.269%	371
Admixed American	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.00878%	11,384
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
East Asian	0.00223%	44,852
European (non-Finnish)	0.000678%	147,495

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.Ala4483=
Coding: c.13449G>A
MANE Select: NM_000384
dbSNP: rs138421941
Type: single nucleotide variant
Location: chr2:21001973 (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.Ala4483Glu Uncertain significance ★ ⚠ same residue
APOB p.Ala4483Val Conflicting classifications of pathogenicity ★ ⚠ same residue
APOB p.Ala4483Ser Likely benign ★ 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

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-ala4483 (accessed [today's date]).

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