Is ABCB4 p.Asp378= (c.1134C>T) pathogenic?

ABCB4 p.Asp378= (c.1134C>T) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-21). Absent from gnomAD v4.1; Associated with progressive familial intrahepatic cholestasis type 3.

What condition is associated with ABCB4 p.Asp378= (c.1134C>T)?

ABCB4 p.Asp378= (c.1134C>T) is associated with progressive familial intrahepatic cholestasis type 3 (ClinVar).

How common is ABCB4 p.Asp378= (c.1134C>T) in the general population?

ABCB4 p.Asp378= (c.1134C>T) is absent from gnomAD v4.1 (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

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

ABCB4 p.Asp378=

c.1134C>T · rs1811153797 · VCV1028758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

progressive familial intrahepatic cholestasis type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.34 · evaluated, not missing
Pangolin	Δ0.20	loss · gain 0.11 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Overall
CADD	13.43	PHRED · no single calibrated threshold — expert panels disagree

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.Asp378=
Coding: c.1134C>T
MANE Select: NM_000443
dbSNP: rs1811153797
Type: single nucleotide variant
Location: chr7:87443759 (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

progressive familial intrahepatic cholestasis type 3 — 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

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.3081+1G>C Pathogenic ★★ same condition
ABCB4 c.3486+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.834-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg1046Ter Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg144Ter 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-asp378 (accessed [today's date]).

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