Is ABCB11 p.Lys930fs (c.2783_2787dup) pathogenic?

ABCB11 p.Lys930fs (c.27832787dup) is classified Pathogenic in ABCB11 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-14). Very rare (popmax 0.00102%, nfe); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Lys930fs (c.2783_2787dup)?

ABCB11 p.Lys930fs (c.2783_2787dup) is associated with familial intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2, benign recurrent intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Lys930fs (c.2783_2787dup) in the general population?

ABCB11 p.Lys930fs (c.2783_2787dup) is very rare (popmax 0.00102%, nfe) (gnomAD).

ABCB11 p.Lys930fs

c.2783_2787dup · rs752919965 · VCV6594

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 2.1, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,828 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,742 alleles · very rare

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.Lys930fs
Coding: c.2783_2787dup
MANE Select: NM_003742
dbSNP: rs752919965
Type: Duplication
Location: chr2:168936256 (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 930: an α-helix; the abc transmembrane type-1 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

Also linked: progressive familial intrahepatic cholestasis type 2 benign recurrent intrahepatic cholestasis type 2

Similar variants

ABCB11 p.Gly296fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Gly344fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Phe774fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Thr625fs Pathogenic ★★ same condition
ABCB11 p.Val1257fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Val597fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.77-16dup Benign/Likely benign ★★ same condition
ABCB11 c.1435-17_1450dup 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-lys930fs (accessed [today's date]).

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