Is APOB p.Pro2027= (c.6081A>G) pathogenic?

APOB p.Pro2027= (c.6081A>G) is classified Likely benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). Very rare (popmax 0.0011%, nfe); Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Pro2027= (c.6081A>G)?

APOB p.Pro2027= (c.6081A>G) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Pro2027= (c.6081A>G) in the general population?

APOB p.Pro2027= (c.6081A>G) is very rare (popmax 0.0011%, nfe) (gnomAD).

APOB p.Pro2027=

c.6081A>G · rs773772203 · VCV2923761

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

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 -5.9	GERP -2.1
Overall
CADD	0.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,180,012 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000805% 13/1,614,030 alleles · very rare exomes 8/1,461,854 · genomes 5/152,176 · joint denominator

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.Pro2027=
Coding: c.6081A>G
MANE Select: NM_000384
dbSNP: rs773772203
Type: single nucleotide variant
Location: chr2:21010787 (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

hypercholesterolemia, autosomal dominant, type B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypobetalipoproteinemia 1

Similar variants

APOB p.Pro2027Gln Conflicting classifications of pathogenicity ★ same residue
APOB p.Pro2027Ser Uncertain significance ★ 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-pro2027 (accessed [today's date]).

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