Is ABCB4 p.Ala737= (c.2211G>C) pathogenic?

ABCB4 p.Ala737= (c.2211G>C) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). Absent from gnomAD v4.1; Associated with gallbladder disease 1.

What condition is associated with ABCB4 p.Ala737= (c.2211G>C)?

ABCB4 p.Ala737= (c.2211G>C) is associated with gallbladder disease 1, progressive familial intrahepatic cholestasis type 3, cholestasis, intrahepatic, of pregnancy, 3 (ClinVar).

How common is ABCB4 p.Ala737= (c.2211G>C) in the general population?

ABCB4 p.Ala737= (c.2211G>C) is absent from gnomAD v4.1 (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.Ala737=

c.2211G>C · VCV3779320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

gallbladder disease 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.61	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.42	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.8	GERP -3.7
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB4
Protein: p.Ala737=
Coding: c.2211G>C
MANE Select: NM_000443
Type: single nucleotide variant
Location: chr7:87423906 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 737: a UniProt-annotated variant site (in pfic3); 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

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

For Low phospholipid-associated cholelithiasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult

Similar variants

ABCB4 p.Ala737Val 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.2211+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A Pathogenic ★★ same condition
ABCB4 c.3081+1G>C Pathogenic ★★ same condition
ABCB4 c.3486+1G>A 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-ala737 (accessed [today's date]).

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