Is ABCB4 p.Lys577= (c.1731G>A) pathogenic?

ABCB4 p.Lys577= (c.1731G>A) is classified Uncertain significance in ABCB4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-14). Very rare (popmax 8.47e-05%, nfe); Associated with gallbladder disease 1.

What condition is associated with ABCB4 p.Lys577= (c.1731G>A)?

ABCB4 p.Lys577= (c.1731G>A) is associated with gallbladder disease 1 (ClinVar).

How common is ABCB4 p.Lys577= (c.1731G>A) in the general population?

ABCB4 p.Lys577= (c.1731G>A) is very rare (popmax 8.47e-05%, 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.Lys577=

c.1731G>A · VCV4532080

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

gallbladder disease 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.93	donor loss · deltas
Pangolin	Δ0.81	loss · gain 0.54 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 0.99, phastCons 1
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.84e-05% 1/1,461,864 alleles · very rare

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.Lys577=
Coding: c.1731G>A
MANE Select: NM_000443
Type: single nucleotide variant
Location: chr7:87439667 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 577: an α-helix; the abc transporter 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

For Low phospholipid-associated cholelithiasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult

Similar variants

CROT p.Ala577Gly Uncertain significance ★ ⚠ same residue
ABCB4 c.1356+2T>C Pathogenic/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.3486+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.3486+5G>A Likely pathogenic ★★ same condition
ABCB4 c.80+1G>A 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-lys577 (accessed [today's date]).

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