Is APOB p.Ile3936= (c.11808C>T) pathogenic?

APOB p.Ile3936= (c.11808C>T) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Common (popmax 5.28%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial hypercholesterolemia.

What condition is associated with APOB p.Ile3936= (c.11808C>T)?

APOB p.Ile3936= (c.11808C>T) is associated with familial hypercholesterolemia, hypercholesterolemia, familial, 1, hypercholesterolemia, autosomal dominant, type B (ClinVar).

APOB p.Ile3936=

Q: How common is APOB p.Ile3936= (c.11808C>T) in the general population?

APOB p.Ile3936= (c.11808C>T) is common (popmax 5.28%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.11808C>T · rs12720852 · VCV255974

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 5.28%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.23	GERP -3.4, phastCons 0.002
Overall
CADD	0.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.28% African / African-American · 3,957/74,918 alleles

Filtering AF 5.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.09%

Overall 0.277% 4,476/1,613,386 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.28%	19
Admixed American	0.325%	308
Remaining individualsnot grpmax-eligible	0.325%	308
Middle Eastern	0.281%	356
European (non-Finnish)	0.00797%	12,548
South Asian	0.00769%	13,009
Finnishnot grpmax-eligible	0.00469%	21,335

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.Ile3936=
Coding: c.11808C>T
MANE Select: NM_000384
dbSNP: rs12720852
Type: single nucleotide variant
Location: chr2:21004656 (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, familial, 1 hypercholesterolemia, autosomal dominant, type B familial hypobetalipoproteinemia 1

Similar variants

APOB p.Ile3936Met 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-ile3936 (accessed [today's date]).

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