Is ABCB4 p.Arg1013= (c.3037A>C) pathogenic?

ABCB4 p.Arg1013= (c.3037A>C) is classified Conflicting classifications of pathogenicity in ABCB4 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-04-14). Rare (popmax 0.25%, nfe); Associated with gallbladder disease 1.

What condition is associated with ABCB4 p.Arg1013= (c.3037A>C)?

ABCB4 p.Arg1013= (c.3037A>C) is associated with gallbladder disease 1, progressive familial intrahepatic cholestasis type 3, cholestasis, intrahepatic, of pregnancy, 3 (ClinVar).

How common is ABCB4 p.Arg1013= (c.3037A>C) in the general population?

ABCB4 p.Arg1013= (c.3037A>C) is rare (popmax 0.25%, nfe) (gnomAD).

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.Arg1013=

c.3037A>C · rs2230029 · VCV282951

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.25%, nfe)

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 5.1	GERP 1.9, phastCons 1
Overall
CADD	9.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.25% European (non-Finnish) · 2,955/1,180,008 alleles

Filtering AF 0.243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.24%

Overall 0.202% 3,263/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.25%	399
Remaining individualsnot grpmax-eligible	0.134%	744
Finnishnot grpmax-eligible	0.131%	762
South Asian	0.0725%	1,380
Admixed American	0.06%	1,667
African / African-American	0.048%	2,085
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802

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.Arg1013=
Coding: c.3037A>C
MANE Select: NM_000443
dbSNP: rs2230029
Type: single nucleotide variant
Location: chr7:87409280 (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

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 p.Arg1013Lys Uncertain significance ★ ⚠ 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-arg1013 (accessed [today's date]).

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