Is APOB p.Asp4017= (c.12051C>T) pathogenic?

APOB p.Asp4017= (c.12051C>T) is classified Conflicting classifications of pathogenicity in APOB (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-08). Ultra-rare (popmax 0.032%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Asp4017= (c.12051C>T)?

APOB p.Asp4017= (c.12051C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Asp4017= (c.12051C>T) in the general population?

APOB p.Asp4017= (c.12051C>T) is ultra-rare (popmax 0.032%, afr) (gnomAD).

APOB p.Asp4017=

c.12051C>T · rs12713501 · VCV695320

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, 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 -0.56	GERP -3.3
Overall
CADD	0.364	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/74,888 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00372% 60/1,613,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,120
Admixed American	0.00334%	29,983
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)	0.00271%	36,872

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.Asp4017=
Coding: c.12051C>T
MANE Select: NM_000384
dbSNP: rs12713501
Type: single nucleotide variant
Location: chr2:21004305 (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 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-asp4017 (accessed [today's date]).

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