Is ABCC2 p.Thr482= (c.1446C>G) pathogenic?

ABCC2 p.Thr482= (c.1446C>G) is classified Benign/Likely benign in ABCC2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.26%, nfe); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Thr482= (c.1446C>G)?

ABCC2 p.Thr482= (c.1446C>G) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Thr482= (c.1446C>G) in the general population?

ABCC2 p.Thr482= (c.1446C>G) is low-frequency (popmax 1.26%, nfe) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Thr482=

c.1446C>G · rs113646094 · VCV255993

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.26%, nfe)

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 0.59	GERP -0.28, phastCons 0.33
Overall
CADD	6.738	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.26% European (non-Finnish) · 14,924/1,179,966 alleles

Filtering AF 1.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.24%

Overall 1.14% 18,420/1,613,976 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.93%	34
European (non-Finnish)grpmax	1.26%	79
Ashkenazi Jewishnot grpmax-eligible	1.22%	82
Remaining individualsnot grpmax-eligible	0.893%	112
Amishnot grpmax-eligible	0.439%	228
Admixed American	0.41%	244
Middle Eastern	0.33%	303
South Asian	0.294%	340
African / African-American	0.22%	455

Finnish 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.Thr482=
Coding: c.1446C>G
MANE Select: NM_000392
dbSNP: rs113646094
Type: single nucleotide variant
Location: chr10:99804255 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 482: an α-helix; the abc transmembrane type-1 1 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-thr482 (accessed [today's date]).

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