Is ABCC2 p.Leu788fs (c.2362_2363del) pathogenic?

ABCC2 p.Leu788fs (c.23622363del) is classified Pathogenic/Likely pathogenic in ABCC2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-24). Ultra-rare (popmax 0.0263%, sas); Associated with ABCC2-related disorder.

What condition is associated with ABCC2 p.Leu788fs (c.2362_2363del)?

ABCC2 p.Leu788fs (c.2362_2363del) is associated with ABCC2-related disorder, Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Leu788fs (c.2362_2363del) in the general population?

ABCC2 p.Leu788fs (c.2362_2363del) is ultra-rare (popmax 0.0263%, sas) (gnomAD).

ABCC2 p.Leu788fs

c.2362_2363del · rs772673105 · VCV298456

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, sas)

Conditions

ABCC2-related disorder

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 18 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.8	GERP -5.4
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 0.0263% South Asian · 24/91,082 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.00211% 34/1,614,162 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0263%	3,795
East Asian	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.000508%	196,672

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.Leu788fs
Coding: c.2362_2363del
MANE Select: NM_000392
dbSNP: rs772673105
Type: Deletion
Location: chr10:99818880 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 788: an α-helix; the abc transporter 1 domain

Full ABCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCC2-related disorder

Also linked: Dubin-Johnson syndrome

Similar variants

ABCC2 p.Asn718fs Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Leu809fs Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Pro194_Ser195insTer Pathogenic ★★ same condition
ABCC2 p.Tyr1134fs Pathogenic ★★ same condition
ABCC2 p.Val1114fs Pathogenic/Likely 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

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-leu788fs (accessed [today's date]).

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