Is APOB p.Glu3493= (c.10479G>A) pathogenic?

APOB p.Glu3493= (c.10479G>A) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-17). Rare (popmax 0.259%, afr); Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Glu3493= (c.10479G>A)?

APOB p.Glu3493= (c.10479G>A) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypercholesterolemia, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Glu3493= (c.10479G>A) in the general population?

APOB p.Glu3493= (c.10479G>A) is rare (popmax 0.259%, afr) (gnomAD).

APOB p.Glu3493=

c.10479G>A · rs113096093 · VCV477788

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.259%, afr)

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 -0.077	GERP -1.1, phastCons 0.57
Overall
CADD	2.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.259% African / African-American · 194/75,018 alleles

Filtering AF 0.229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.217%

Overall 0.0139% 225/1,614,036 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.259%	387
Admixed American	0.03%	3,333
Remaining individualsnot grpmax-eligible	0.0208%	4,808

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.Glu3493=
Coding: c.10479G>A
MANE Select: NM_000384
dbSNP: rs113096093
Type: single nucleotide variant
Location: chr2:21006389 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3493: the 'heparin-binding' region

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 p.Glu3493Ala Uncertain significance ★ ⚠ same residue
APOB p.Glu3493Lys 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

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-glu3493 (accessed [today's date]).

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