Is ABCC2 p.Ile982Val (c.2944A>G) pathogenic?

ABCC2 p.Ile982Val (c.2944A>G) is classified Likely benign in ABCC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0779); Rare (popmax 0.452%, afr); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Ile982Val (c.2944A>G)?

ABCC2 p.Ile982Val (c.2944A>G) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Ile982Val (c.2944A>G) in the general population?

ABCC2 p.Ile982Val (c.2944A>G) is rare (popmax 0.452%, afr) (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.Ile982Val (c.2944A>G)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

ABCC2 p.Ile982Val

c.2944A>G · rs17222554 · VCV282330

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.452%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.4
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	0.852	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 0.452% African / African-American · 339/75,026 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.397%

Overall 0.0243% 392/1,614,162 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.452%	221
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Admixed American	0.0417%	2,401
Middle Eastern	0.0165%	6,062

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.Ile982Val
Coding: c.2944A>G
MANE Select: NM_000392
dbSNP: rs17222554
Type: single nucleotide variant
Location: chr10:99831671 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 982: an α-helix; the abc transmembrane type-1 2 domain; a UniProt-annotated variant site (in)

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-ile982val (accessed [today's date]).

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