Is APOB p.Asn3580= (c.10740C>T) pathogenic?

APOB p.Asn3580= (c.10740C>T) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0607%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Asn3580= (c.10740C>T)?

APOB p.Asn3580= (c.10740C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is APOB p.Asn3580= (c.10740C>T) in the general population?

APOB p.Asn3580= (c.10740C>T) is ultra-rare (popmax 0.0607%, nfe) (gnomAD).

APOB p.Asn3580=

c.10740C>T · rs150312765 · VCV495856

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0607%, 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 -3.6	GERP -3.4
Overall
CADD	0.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0607% European (non-Finnish) · 716/1,179,954 alleles

Filtering AF 0.0569% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0555%

Overall 0.0459% 741/1,613,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0607%	1,648
Remaining individualsnot grpmax-eligible	0.0224%	4,462
African / African-American	0.00801%	12,479
Admixed American	0.005%	19,984
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
South Asian	0.0011%	91,066

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.Asn3580=
Coding: c.10740C>T
MANE Select: NM_000384
dbSNP: rs150312765
Type: single nucleotide variant
Location: chr2:21006128 (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, familial, 1 hypercholesterolemia, autosomal dominant, type B familial hypobetalipoproteinemia 1

Similar variants

APOB p.Asn3580Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
APOB p.Asn3580Ser 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-asn3580 (accessed [today's date]).

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