Is ABCB4 p.Asn168= (c.504C>T) pathogenic?

ABCB4 p.Asn168= (c.504C>T) is classified Benign/Likely benign in ABCB4 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-04-14). Common (popmax 56.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with gallbladder disease 1.

What condition is associated with ABCB4 p.Asn168= (c.504C>T)?

ABCB4 p.Asn168= (c.504C>T) is associated with gallbladder disease 1, progressive familial intrahepatic cholestasis type 3, cholestasis, intrahepatic, of pregnancy, 3 (ClinVar).

How is Low phospholipid-associated cholelithiasis inherited?

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

ABCB4 p.Asn168=

Q: How common is ABCB4 p.Asn168= (c.504C>T) in the general population?

ABCB4 p.Asn168= (c.504C>T) is common (popmax 56.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.504C>T · rs1202283 · VCV198082

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 56.1%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

gallbladder disease 1

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 -7.3	GERP -3.7
Overall
CADD	0.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 56.1% European (non-Finnish) · 661,075/1,179,324 alleles

Filtering AF 55.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.9%

Overall 52% 838,449/1,613,056 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	64%	2
Amishnot grpmax-eligible	63.7%	2
European (non-Finnish)grpmax	56.1%	2
Remaining individualsnot grpmax-eligible	47.9%	2
Admixed American	44.8%	2
South Asian	44.2%	2
Middle Eastern	44%	2
East Asian	39.2%	3
Ashkenazi Jewishnot grpmax-eligible	38.8%	3
African / African-American	9.52%	11

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn168=
Coding: c.504C>T
MANE Select: NM_000443
dbSNP: rs1202283
Type: single nucleotide variant
Location: chr7:87452976 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 168: the abc transmembrane type-1 1 domain

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

Disease context

gallbladder disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive familial intrahepatic cholestasis type 3 cholestasis, intrahepatic, of pregnancy, 3 familial intrahepatic cholestasis

For Low phospholipid-associated cholelithiasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
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.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-asn168 (accessed [today's date]).

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