Is APOB p.Ser595= (c.1785C>G) pathogenic?

APOB p.Ser595= (c.1785C>G) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.78%, amr); Associated with hypercholesterolemia, autosomal dominant, type B.

What condition is associated with APOB p.Ser595= (c.1785C>G)?

APOB p.Ser595= (c.1785C>G) is associated with hypercholesterolemia, autosomal dominant, type B, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is APOB p.Ser595= (c.1785C>G) in the general population?

APOB p.Ser595= (c.1785C>G) is low-frequency (popmax 3.78%, amr) (gnomAD).

APOB p.Ser595=

c.1785C>G · rs139864087 · VCV334171

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.78%, amr)

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 1.4	GERP 0.72, phastCons 1
Overall
CADD	8.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.78% Admixed American · 2,266/60,020 alleles

Filtering AF 3.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.59%

Overall 0.148% 2,387/1,614,142 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.78%	26
Remaining individualsnot grpmax-eligible	0.0976%	1,025
African / African-American	0.056%	1,786
European (non-Finnish)	0.00153%	65,557

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.Ser595=
Coding: c.1785C>G
MANE Select: NM_000384
dbSNP: rs139864087
Type: single nucleotide variant
Location: chr2:21028371 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 595: the vitellogenin domain

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 hypercholesterolemia hypercholesterolemia, familial, 1 familial hypobetalipoproteinemia 1

Similar variants

APOB p.Ser595Phe 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
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-ser595 (accessed [today's date]).

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