Is APOB p.Ser1281= (c.3843C>T) pathogenic?

APOB p.Ser1281= (c.3843C>T) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-11). Rare (popmax 0.774%, afr); Associated with familial hypercholesterolemia.

What condition is associated with APOB p.Ser1281= (c.3843C>T)?

APOB p.Ser1281= (c.3843C>T) is associated with familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Ser1281= (c.3843C>T) in the general population?

APOB p.Ser1281= (c.3843C>T) is rare (popmax 0.774%, afr) (gnomAD).

APOB p.Ser1281=

c.3843C>T · rs72653079 · VCV334149

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.774%, afr)

Conditions

familial hypercholesterolemia

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 0.16	GERP -0.82, phastCons 0.2
Overall
CADD	6.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.774% African / African-American · 581/75,020 alleles

Filtering AF 0.722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.702%

Overall 0.0441% 712/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.774%	129
Remaining individualsnot grpmax-eligible	0.0848%	1,179
Admixed American	0.0716%	1,396
Middle Eastern	0.0666%	1,502
South Asian	0.011%	9,107
East Asian	0.00223%	44,872
European (non-Finnish)	0.00169%	59,001

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.Ser1281=
Coding: c.3843C>T
MANE Select: NM_000384
dbSNP: rs72653079
Type: single nucleotide variant
Location: chr2:21013533 (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

familial hypercholesterolemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 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-ser1281 (accessed [today's date]).

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