Is ABCB4 p.Thr775= (c.2325G>C) pathogenic?

ABCB4 p.Thr775= (c.2325G>C) is classified Benign/Likely benign in ABCB4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-14). Low-frequency (popmax 3.63%, afr); Associated with progressive familial intrahepatic cholestasis type 3.

What condition is associated with ABCB4 p.Thr775= (c.2325G>C)?

ABCB4 p.Thr775= (c.2325G>C) is associated with progressive familial intrahepatic cholestasis type 3, gallbladder disease 1, cholestasis, intrahepatic, of pregnancy, 3 (ClinVar).

How common is ABCB4 p.Thr775= (c.2325G>C) in the general population?

ABCB4 p.Thr775= (c.2325G>C) is low-frequency (popmax 3.63%, afr) (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

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

ABCB4 p.Thr775=

c.2325G>C · rs8187802 · VCV382988

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.63%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.4
Overall
CADD	0.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.63% African / African-American · 2,719/75,000 alleles

Filtering AF 3.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.47%

Overall 0.203% 3,270/1,613,956 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.63%	28
Admixed American	0.267%	375
Remaining individualsnot grpmax-eligible	0.264%	379
Middle Eastern	0.148%	674
European (non-Finnish)	0.018%	5,566
Finnishnot grpmax-eligible	0.00469%	21,340
South Asian	0.0022%	45,536

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.Thr775=
Coding: c.2325G>C
MANE Select: NM_000443
dbSNP: rs8187802
Type: single nucleotide variant
Location: chr7:87420067 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 775: a UniProt-annotated variant site (found in patients with cholangitis; uncertain significance); an α-helix; the abc transmembrane type-1 2 domain

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

Also linked: gallbladder disease 1 cholestasis, intrahepatic, of pregnancy, 3 familial intrahepatic cholestasis

For Progressive familial intrahepatic cholestasis (Orphanet):

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

Similar variants

ABCB4 p.Thr775Met Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-thr775 (accessed [today's date]).

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