Is ABCC2 p.Lys298fs (c.890dup) pathogenic?

ABCC2 p.Lys298fs (c.890dup) is classified Pathogenic in ABCC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-22). Very rare (popmax 0.00334%, amr); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Lys298fs (c.890dup)?

ABCC2 p.Lys298fs (c.890dup) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Lys298fs (c.890dup) in the general population?

ABCC2 p.Lys298fs (c.890dup) is very rare (popmax 0.00334%, amr) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Lys298fs

c.890dup · rs759781877 · VCV2990445

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9	GERP 2.5, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,946 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,613,350 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,973
African / African-American	0.00134%	74,788
South Asian	0.0011%	91,056
European (non-Finnish)	0.000424%	235,969

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.Lys298fs
Coding: c.890dup
MANE Select: NM_000392
dbSNP: rs759781877
Type: Duplication
Location: chr10:99799221 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB

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.Asp1073Ter Pathogenic ★★ same condition
ABCC2 p.Leu1213fs Pathogenic ★★ same condition
ABCC2 p.Val667fs Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Asp304fs Likely pathogenic ★ same condition
ABCC2 p.Thr1251fs Likely pathogenic ★ same condition
ABCC2 p.Tyr119fs Pathogenic ★ same condition
ABCC2 p.Tyr1309fs Likely pathogenic ★ same condition
ABCC2 c.1031+4A>G 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-lys298fs (accessed [today's date]).

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