Is ABCC2 p.Arg393= (c.1179G>A) pathogenic?

ABCC2 p.Arg393= (c.1179G>A) is classified Conflicting classifications of pathogenicity in ABCC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-07). Ultra-rare (popmax 0.0133%, amr); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Arg393= (c.1179G>A)?

ABCC2 p.Arg393= (c.1179G>A) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Arg393= (c.1179G>A) in the general population?

ABCC2 p.Arg393= (c.1179G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Arg393=

c.1179G>A · rs200104823 · VCV879761

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 0.8, phastCons 1
Overall
CADD	3.426	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,010 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000929% 15/1,614,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,501
Remaining individualsnot grpmax-eligible	0.0112%	8,929

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.Arg393=
Coding: c.1179G>A
MANE Select: NM_000392
dbSNP: rs200104823
Type: single nucleotide variant
Location: chr10:99800533 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 393: 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 p.Arg393Trp Pathogenic/Likely pathogenic ★★ same residue
ABCC2 p.Arg393Gln Uncertain significance ★★ ⚠ same residue
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

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-arg393 (accessed [today's date]).

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