Is ABCB4 p.Trp12Ter (c.36G>A) pathogenic?

ABCB4 p.Trp12Ter (c.36G>A) is classified Likely pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). Absent from gnomAD v4.1; Associated with cholestasis, intrahepatic, of pregnancy, 3.

What condition is associated with ABCB4 p.Trp12Ter (c.36G>A)?

ABCB4 p.Trp12Ter (c.36G>A) is associated with cholestasis, intrahepatic, of pregnancy, 3, gallbladder disease 1, progressive familial intrahepatic cholestasis type 3 (ClinVar).

How common is ABCB4 p.Trp12Ter (c.36G>A) in the general population?

ABCB4 p.Trp12Ter (c.36G>A) is absent from gnomAD v4.1 (gnomAD).

How is Intrahepatic cholestasis of pregnancy inherited?

Typically Multigenic/multifactorial, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

ABCB4 p.Trp12Ter

c.36G>A · VCV4850588

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cholestasis, intrahepatic, of pregnancy, 3

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 in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 28
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP 0.69
Overall
CADD	34.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB4
Protein: p.Trp12Ter
Coding: c.36G>A
MANE Select: NM_000443
Type: single nucleotide variant
Location: chr7:87475430 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB

Full ABCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cholestasis, intrahepatic, of pregnancy, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gallbladder disease 1 progressive familial intrahepatic cholestasis type 3

For Intrahepatic cholestasis of pregnancy (Orphanet):

Inheritance: Multigenic/multifactorial, Not applicable
Onset: Adult

Similar variants

ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.1560+1G>A Likely pathogenic ★★ same condition
ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A Pathogenic ★★ same condition
ABCB4 c.3081+1G>C Pathogenic ★★ same condition
ABCB4 c.3486+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.3486+5G>A 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/abcb4-p-trp12ter (accessed [today's date]).

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