Is ABCC2 p.Lys53= (c.159A>G) pathogenic?

ABCC2 p.Lys53= (c.159A>G) is classified Benign/Likely benign in ABCC2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Low-frequency (popmax 4.45%, mid); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Lys53= (c.159A>G)?

ABCC2 p.Lys53= (c.159A>G) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Lys53= (c.159A>G) in the general population?

ABCC2 p.Lys53= (c.159A>G) is low-frequency (popmax 4.45%, mid) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Lys53=

c.159A>G · rs17222596 · VCV286427

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.45%, mid)

Conditions

Dubin-Johnson syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.1	GERP -0.86, phastCons 1
Overall
CADD	7.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.45% Middle Eastern · 270/6,062 alleles

Filtering AF 4.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.85%

Overall 0.186% 3,000/1,614,110 alleles · low-frequency exomes 2,687/1,461,880 · genomes 313/152,230 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	4.45%	22
Ashkenazi Jewishnot grpmax-eligible	2.2%	45
Admixed American	0.463%	216
Remaining individualsnot grpmax-eligible	0.41%	244
European (non-Finnish)	0.122%	821
African / African-American	0.068%	1,471
South Asian	0.0571%	1,752
Finnishnot grpmax-eligible	0.00781%	12,806

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: ABCC2
Protein: p.Lys53=
Coding: c.159A>G
MANE Select: NM_000392
dbSNP: rs17222596
Type: single nucleotide variant
Location: chr10:99784733 (GRCh38)

Full ABCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Dubin-Johnson syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dubin-Johnson syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult

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/abcc2-p-lys53 (accessed [today's date]).

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