Is ABCB11 p.Lys1145= (c.3435A>G) pathogenic?

ABCB11 p.Lys1145= (c.3435A>G) is classified Benign/Likely benign in ABCB11 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-14). Rare (popmax 0.3%, afr); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Lys1145= (c.3435A>G)?

ABCB11 p.Lys1145= (c.3435A>G) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Lys1145= (c.3435A>G) in the general population?

ABCB11 p.Lys1145= (c.3435A>G) is rare (popmax 0.3%, afr) (gnomAD).

ABCB11 p.Lys1145=

c.3435A>G · rs11568366 · VCV283582

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.3%, afr)

Conditions

familial intrahepatic cholestasis

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 1.5	GERP -3, phastCons 0.97
Overall
CADD	5.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.3% African / African-American · 225/75,038 alleles

Filtering AF 0.268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.255%

Overall 0.0146% 236/1,613,808 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.3%	334
Remaining individualsnot grpmax-eligible	0.0112%	8,927
Admixed American	0.00667%	15,004

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: ABCB11
Protein: p.Lys1145=
Coding: c.3435A>G
MANE Select: NM_003742
dbSNP: rs11568366
Type: single nucleotide variant
Location: chr2:168927339 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB
Residue 1145: a turn; the abc transporter 2 domain

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1638+1G>C Likely pathogenic ★★ same condition
ABCB11 c.2012-2A>G Pathogenic ★★ same condition
ABCB11 c.2012-8T>G 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/abcb11-p-lys1145 (accessed [today's date]).

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