Is ABCB4 p.Arg144Ter (c.430C>T) pathogenic?

ABCB4 p.Arg144Ter (c.430C>T) is classified Pathogenic in ABCB4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-14). Ultra-rare (popmax 0.0164%, mid); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB4 p.Arg144Ter (c.430C>T)?

ABCB4 p.Arg144Ter (c.430C>T) is associated with familial intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 3, cholestasis, intrahepatic, of pregnancy, 3 (ClinVar).

How common is ABCB4 p.Arg144Ter (c.430C>T) in the general population?

ABCB4 p.Arg144Ter (c.430C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ABCB4 p.Arg144Ter

c.430C>T · rs72552780 · VCV13696

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

familial intrahepatic cholestasis

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 6 of 28
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.9, phastCons 1
Overall
CADD	46.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000372% 6/1,613,632 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00401%	24,919
Admixed American	0.00334%	29,973

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: ABCB4
Protein: p.Arg144Ter
Coding: c.430C>T
MANE Select: NM_000443
dbSNP: rs72552780
Type: single nucleotide variant
Location: chr7:87453050 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 144: an α-helix; the abc transmembrane type-1 1 domain

Full ABCB4 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 3 cholestasis, intrahepatic, of pregnancy, 3

Similar variants

ABCB4 p.Arg144Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB4 p.Arg144Gly Uncertain significance ★ ⚠ same residue
ABCB4 c.1560+1G>A Likely pathogenic ★★ same condition
ABCB4 c.2064+3A>T 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.2783+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A 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-arg144ter (accessed [today's date]).

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