Is ABCC2 p.Ile1132= (c.3396T>C) pathogenic?

ABCC2 p.Ile1132= (c.3396T>C) is classified Benign in ABCC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.12%, mid); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Ile1132= (c.3396T>C)?

ABCC2 p.Ile1132= (c.3396T>C) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Ile1132= (c.3396T>C) in the general population?

ABCC2 p.Ile1132= (c.3396T>C) is low-frequency (popmax 1.12%, mid) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Ile1132=

c.3396T>C · rs17216345 · VCV771742

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, mid)

Conditions

Dubin-Johnson syndrome

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 -0.49	GERP -5.1
Overall
CADD	4.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.12% Middle Eastern · 68/6,062 alleles

Filtering AF 0.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.928%

Overall 0.491% 7,930/1,614,172 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.12%	89
South Asian	1%	100
European (non-Finnish)	0.52%	192
Remaining individualsnot grpmax-eligible	0.464%	216
Finnishnot grpmax-eligible	0.454%	220
Admixed American	0.218%	458
Ashkenazi Jewishnot grpmax-eligible	0.182%	548
African / African-American	0.064%	1,563
East Asian	0.00446%	22,439

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.Ile1132=
Coding: c.3396T>C
MANE Select: NM_000392
dbSNP: rs17216345
Type: single nucleotide variant
Location: chr10:99834517 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1132: an α-helix; the abc transmembrane type-1 2 domain

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

Similar variants

ABCC2 c.1031+4A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.3258+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.333+1G>A Likely pathogenic ★★ same condition
ABCC2 c.3415-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.3741+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.3741+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.576+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg1066Ter 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/abcc2-p-ile1132 (accessed [today's date]).

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