Is ABCB4 p.Ile237= (c.711A>T) pathogenic?

ABCB4 p.Ile237= (c.711A>T) is classified Benign/Likely benign in ABCB4 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-04-14). Common (popmax 31.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with gallbladder disease 1.

What condition is associated with ABCB4 p.Ile237= (c.711A>T)?

ABCB4 p.Ile237= (c.711A>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.Ile237=

Q: How common is ABCB4 p.Ile237= (c.711A>T) in the general population?

ABCB4 p.Ile237= (c.711A>T) is common (popmax 31.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.711A>T · rs2109505 · VCV256166

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 31.5%, afr) — 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 0.004	GERP -3.7, phastCons 0.75
Overall
CADD	8.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.5% African / African-American · 23,614/74,912 alleles

Filtering AF 31.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 31%

Overall 19.3% 312,076/1,613,670 alleles · common exomes 278,276/1,461,620 · genomes 33,800/152,050 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.5%	3
East Asian	27.1%	4
South Asian	24.1%	4
Middle Eastern	21%	5
Remaining individualsnot grpmax-eligible	20.3%	5
Ashkenazi Jewishnot grpmax-eligible	20%	5
Finnishnot grpmax-eligible	19.7%	5
Admixed American	19.2%	5
European (non-Finnish)	17.8%	6
Amishnot grpmax-eligible	16.7%	6

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.Ile237=
Coding: c.711A>T
MANE Select: NM_000443
dbSNP: rs2109505
Type: single nucleotide variant
Location: chr7:87450090 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 237: 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

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.Ile237Leu Uncertain significance ★ ⚠ same residue
CROT p.Ile237Thr 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

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-ile237 (accessed [today's date]).

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