Is ABCC2 p.Val1114fs (c.3337del) pathogenic?

ABCC2 p.Val1114fs (c.3337del) is classified Pathogenic/Likely pathogenic in ABCC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0209%, sas); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Val1114fs (c.3337del)?

ABCC2 p.Val1114fs (c.3337del) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Val1114fs (c.3337del) in the general population?

ABCC2 p.Val1114fs (c.3337del) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Val1114fs

c.3337del · rs775771081 · VCV426249

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

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 24 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 0.46, phastCons 1
Overall
CADD	27.7	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 0.0209% South Asian · 19/91,074 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00124% 20/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,793
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.Val1114fs
Coding: c.3337del
MANE Select: NM_000392
dbSNP: rs775771081
Type: Deletion
Location: chr10:99834456 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1114: an α-helix; the abc transmembrane type-1 2 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.Asn718fs Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Leu788fs Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Pro194_Ser195insTer Pathogenic ★★ same condition
ABCC2 p.Tyr1134fs Pathogenic ★★ same condition
ABCC2 c.4507_4508+2del Uncertain significance ★★ same condition
ABCC2 p.Asn1509fs Likely pathogenic ★ same condition
ABCC2 p.Asn690fs Likely pathogenic ★ same condition
ABCC2 p.Lys1416fs 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-val1114fs (accessed [today's date]).

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