Is ABCC2 p.Lys495Glu (c.1483A>G) pathogenic?

ABCC2 p.Lys495Glu (c.1483A>G) is classified Benign/Likely benign in ABCC2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely pathogenic (0.8653); Rare (popmax 0.426%, sas); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Lys495Glu (c.1483A>G)?

ABCC2 p.Lys495Glu (c.1483A>G) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Lys495Glu (c.1483A>G) in the general population?

ABCC2 p.Lys495Glu (c.1483A>G) is rare (popmax 0.426%, sas) (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.Lys495Glu (c.1483A>G)?

AlphaMissense predicts likely pathogenic (score 0.8653) — an in-silico prediction, not a clinical call.

ABCC2 p.Lys495Glu

c.1483A>G · rs17222561 · VCV193811

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8653 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.426%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
AlphaMissense	0.8653	likely pathogenic
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -16.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	28.2	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 0.426% South Asian · 388/91,062 alleles

Filtering AF 0.392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.388%

Overall 0.401% 6,465/1,613,986 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.4%	71
South Asiangrpmax	0.426%	235
European (non-Finnish)	0.402%	249
Remaining individualsnot grpmax-eligible	0.381%	263
Ashkenazi Jewishnot grpmax-eligible	0.213%	470
Admixed American	0.152%	660
Middle Eastern	0.132%	757
African / African-American	0.052%	1,924
East Asian	0.00223%	44,886

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys495Glu
Coding: c.1483A>G
MANE Select: NM_000392
dbSNP: rs17222561
Type: single nucleotide variant
Location: chr10:99805400 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 495: an α-helix; the abc transmembrane type-1 1 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-lys495glu (accessed [today's date]).

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