Is APOB p.Arg2085= (c.6255A>G) pathogenic?

APOB p.Arg2085= (c.6255A>G) is classified Likely benign in APOB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-15). Ultra-rare (popmax 0.0167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Arg2085= (c.6255A>G)?

APOB p.Arg2085= (c.6255A>G) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Arg2085= (c.6255A>G) in the general population?

APOB p.Arg2085= (c.6255A>G) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

APOB p.Arg2085=

c.6255A>G · rs779753415 · VCV927952

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

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 1.5	GERP 1.6, phastCons 0.04
Overall
CADD	1.186	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,986 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00273% 44/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,999
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00254%	39,334

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.Arg2085=
Coding: c.6255A>G
MANE Select: NM_000384
dbSNP: rs779753415
Type: single nucleotide variant
Location: chr2:21010613 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2085: the 'heparin-binding' region

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.Arg2085Ter Pathogenic/Likely pathogenic ★★ same residue
APOB p.Arg2085Gln 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
APOB p.Arg2513Ter 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-arg2085 (accessed [today's date]).

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