Is ABCC2 p.Arg768Trp (c.2302C>T) pathogenic?

ABCC2 p.Arg768Trp (c.2302C>T) is classified Pathogenic/Likely pathogenic in ABCC2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.9763); Rare (popmax 0.149%, eas); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Arg768Trp (c.2302C>T)?

ABCC2 p.Arg768Trp (c.2302C>T) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Arg768Trp (c.2302C>T) in the general population?

ABCC2 p.Arg768Trp (c.2302C>T) is rare (popmax 0.149%, eas) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

What do computational predictors say about ABCC2 p.Arg768Trp (c.2302C>T)?

AlphaMissense predicts likely pathogenic (score 0.9763) — an in-silico prediction, not a clinical call.

ABCC2 p.Arg768Trp

c.2302C>T · rs56199535 · VCV8412

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.9763 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
AlphaMissense	0.9763	likely pathogenic ✓ concordant with ClinVar · top 4% in ABCC2
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -14.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -0.73, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.149% East Asian · 67/44,878 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.0105% 170/1,614,112 alleles · rare exomes 156/1,461,868 · genomes 14/152,244 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.149%	670
European (non-Finnish)	0.00814%	12,292
African / African-American	0.00533%	18,756
Remaining individualsnot grpmax-eligible	0.0032%	31,256
Admixed American	0.00167%	60,014

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.Arg768Trp
Coding: c.2302C>T
MANE Select: NM_000392
dbSNP: rs56199535
Type: single nucleotide variant
Location: chr10:99818820 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 768: an α-helix; the abc transporter 1 domain; a UniProt-annotated variant site (in djs)

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.Arg768Gln Uncertain significance ★★ ⚠ same residue
ABCC2 p.Arg768Pro Uncertain significance ★ ⚠ same residue
ABCC2 p.Arg768= Likely benign ★ 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

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-arg768trp (accessed [today's date]).

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