Is ABCC2 p.Tyr119fs (c.351_355dup) pathogenic?

ABCC2 p.Tyr119fs (c.351355dup) is classified Pathogenic in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). Very rare (popmax 0.00668%, eas); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Tyr119fs (c.351_355dup)?

ABCC2 p.Tyr119fs (c.351_355dup) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Tyr119fs (c.351_355dup) in the general population?

ABCC2 p.Tyr119fs (c.351_355dup) is very rare (popmax 0.00668%, eas) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Tyr119fs

c.351_355dup · rs1351419381 · VCV1333210

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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 4 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,888 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000205% 3/1,461,834 alleles · very rare

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.Tyr119fs
Coding: c.351_355dup
MANE Select: NM_000392
dbSNP: rs1351419381
Type: Duplication
Location: chr10:99793565 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 119: an α-helix

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.Lys298fs 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.Tyr1309fs Likely pathogenic ★ same condition
ABCC2 p.Tyr119= Likely benign same residue

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-tyr119fs (accessed [today's date]).

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