Is ABCB11 p.Val368Ter (c.1100_1101dup) pathogenic?

ABCB11 p.Val368Ter (c.11001101dup) is classified Likely pathogenic in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-20). Absent from gnomAD; Associated with progressive familial intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Val368Ter (c.1100_1101dup)?

ABCB11 p.Val368Ter (c.1100_1101dup) is associated with progressive familial intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Val368Ter (c.1100_1101dup) in the general population?

ABCB11 p.Val368Ter (c.1100_1101dup) is absent from gnomAD (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCB11 p.Val368Ter

c.1100_1101dup · rs1574462504 · VCV804388

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

progressive familial intrahepatic cholestasis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2	GERP -2.8

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCB11
Protein: p.Val368Ter
Coding: c.1100_1101dup
MANE Select: NM_003742
dbSNP: rs1574462504
Type: Duplication
Location: chr2:168979961 (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 368: an α-helix; the abc transmembrane type-1 1 domain

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

Disease context

progressive familial intrahepatic cholestasis type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive familial intrahepatic cholestasis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

ABCB11 p.Val368fs Pathogenic ★★ same residue
ABCB11 p.Gly344fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Lys930fs 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

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-val368ter (accessed [today's date]).

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