Is ABCC2 p.Ile1324= (c.3972C>T) pathogenic?

ABCC2 p.Ile1324= (c.3972C>T) is classified Benign in ABCC2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 37.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Ile1324= (c.3972C>T)?

ABCC2 p.Ile1324= (c.3972C>T) is associated with Dubin-Johnson syndrome (ClinVar).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Ile1324=

Q: How common is ABCC2 p.Ile1324= (c.3972C>T) in the general population?

ABCC2 p.Ile1324= (c.3972C>T) is common (popmax 37.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3972C>T · rs3740066 · VCV196101

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 37.4%, nfe) — too common for a highly-penetrant pathogenic allele

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 0.35	GERP -0.78, phastCons 0.037
Overall
CADD	9.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 37.4% European (non-Finnish) · 441,164/1,179,858 alleles

Filtering AF 37.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 37.3%

Overall 35.8% 577,792/1,613,504 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	51.1%	2
European (non-Finnish)grpmax	37.4%	3
Remaining individualsnot grpmax-eligible	35.2%	3
Ashkenazi Jewishnot grpmax-eligible	34.8%	3
Admixed American	34.7%	3
Finnishnot grpmax-eligible	34.1%	3
South Asian	32.7%	3
Middle Eastern	32.7%	3
African / African-American	25.8%	4
East Asian	22.9%	4

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile1324=
Coding: c.3972C>T
MANE Select: NM_000392
dbSNP: rs3740066
Type: single nucleotide variant
Location: chr10:99844450 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1324: the abc transporter 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-ile1324 (accessed [today's date]).

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