Is APOB p.Asp728= (c.2184T>C) pathogenic?

APOB p.Asp728= (c.2184T>C) is classified Conflicting classifications of pathogenicity in APOB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-07-16). Very rare (popmax 0.000339%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Asp728= (c.2184T>C)?

APOB p.Asp728= (c.2184T>C) is associated with Cardiovascular phenotype, hypercholesterolemia, familial, 1 (ClinVar).

How common is APOB p.Asp728= (c.2184T>C) in the general population?

APOB p.Asp728= (c.2184T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

APOB p.Asp728=

c.2184T>C · rs1325443043 · VCV523731

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, 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 2	GERP 0.73, phastCons 0.97
Overall
CADD	5.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,942 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,786 alleles · very rare

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.Asp728=
Coding: c.2184T>C
MANE Select: NM_000384
dbSNP: rs1325443043
Type: single nucleotide variant
Location: chr2:21026848 (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, familial, 1

Similar variants

APOB p.Arg3527Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOB p.Arg3527Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOB p.Arg490Trp Pathogenic/Likely pathogenic ★★ same condition
APOB p.Gln1551Ter Pathogenic ★★ same condition
APOB c.1124+3A>G Uncertain significance ★★ same condition
APOB c.11788+4A>G Uncertain significance ★★ same condition
APOB c.12087+2T>C Uncertain significance ★★ same condition
APOB c.1352+60C>A Uncertain significance ★★ 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-asp728 (accessed [today's date]).

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