Is APOB p.Ile3856= (c.11568C>T) pathogenic?

APOB p.Ile3856= (c.11568C>T) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-10). Rare (popmax 0.349%, sas); Associated with familial hypobetalipoproteinemia 1.

What condition is associated with APOB p.Ile3856= (c.11568C>T)?

APOB p.Ile3856= (c.11568C>T) is associated with familial hypobetalipoproteinemia 1, familial hypercholesterolemia, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Ile3856= (c.11568C>T) in the general population?

APOB p.Ile3856= (c.11568C>T) is rare (popmax 0.349%, sas) (gnomAD).

APOB p.Ile3856=

c.11568C>T · rs542175556 · VCV544084

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.349%, sas)

Conditions

familial hypobetalipoproteinemia 1

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 -1.1	GERP -2.5
Overall
CADD	3.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.349% South Asian · 318/91,082 alleles

Filtering AF 0.318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.305%

Overall 0.0211% 341/1,614,042 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.349%	286
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.024%	4,167
African / African-American	0.00133%	75,022
European (non-Finnish)	0.000424%	235,989

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.Ile3856=
Coding: c.11568C>T
MANE Select: NM_000384
dbSNP: rs542175556
Type: single nucleotide variant
Location: chr2:21005300 (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 hypobetalipoproteinemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia hypercholesterolemia, autosomal dominant, type B

Similar variants

APOB p.Ile3856Thr Uncertain significance ★ ⚠ same residue
APOB p.Ile3856Phe 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-ile3856 (accessed [today's date]).

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