Is ABCB4 p.Phe153= (c.459T>C) pathogenic?

ABCB4 p.Phe153= (c.459T>C) is classified Benign in ABCB4 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-14). Common (popmax 5.23%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB4 p.Phe153= (c.459T>C)?

ABCB4 p.Phe153= (c.459T>C) is associated with familial intrahepatic cholestasis, gallbladder disease 1, progressive familial intrahepatic cholestasis type 3 (ClinVar).

ABCB4 p.Phe153=

Q: How common is ABCB4 p.Phe153= (c.459T>C) in the general population?

ABCB4 p.Phe153= (c.459T>C) is common (popmax 5.23%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.459T>C · rs2230027 · VCV256165

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 5.23%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.9, phastCons 1
Overall
CADD	12.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.23% African / African-American · 3,919/74,998 alleles

Filtering AF 5.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.03%

Overall 0.288% 4,643/1,614,072 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.23%	19
Admixed American	0.428%	233
Middle Eastern	0.412%	242
Remaining individualsnot grpmax-eligible	0.336%	298
European (non-Finnish)	0.0184%	5,438
South Asian	0.0154%	6,505
Finnishnot grpmax-eligible	0.00156%	64,024

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.Phe153=
Coding: c.459T>C
MANE Select: NM_000443
dbSNP: rs2230027
Type: single nucleotide variant
Location: chr7:87453021 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 153: 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: gallbladder disease 1 progressive familial intrahepatic cholestasis type 3 cholestasis, intrahepatic, of pregnancy, 3

Similar variants

ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same condition
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
ABCB4 c.3081+1G>C 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-phe153 (accessed [today's date]).

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