Is ABCC2 p.Gln1382Arg (c.4145A>G) pathogenic?

ABCC2 p.Gln1382Arg (c.4145A>G) is classified Likely pathogenic in ABCC2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-05-23). AlphaMissense: likely pathogenic (0.9398); Very rare (popmax 0.00669%, eas); Associated with ABCC2-related disorder.

What condition is associated with ABCC2 p.Gln1382Arg (c.4145A>G)?

ABCC2 p.Gln1382Arg (c.4145A>G) is associated with ABCC2-related disorder, Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Gln1382Arg (c.4145A>G) in the general population?

ABCC2 p.Gln1382Arg (c.4145A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about ABCC2 p.Gln1382Arg (c.4145A>G)?

AlphaMissense predicts likely pathogenic (score 0.9398) — an in-silico prediction, not a clinical call.

ABCC2 p.Gln1382Arg

c.4145A>G · rs72558202 · VCV8416

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9398 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCC2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9398	likely pathogenic ✓ concordant with ClinVar · top 9% in ABCC2
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -14.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Pangolin	Δ0.39	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	33.0	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 0.00669% East Asian · 3/44,832 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000186% 3/1,610,070 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.Gln1382Arg
Coding: c.4145A>G
MANE Select: NM_000392
dbSNP: rs72558202
Type: single nucleotide variant
Location: chr10:99845781 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1382: the abc transporter 2 domain; a UniProt-annotated variant site (in djs)

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.Gln1382Ter Pathogenic/Likely pathogenic ★★ same residue
ABCC2 p.Gln1382Lys Likely pathogenic ★ same residue
ABCC2 c.1031+4A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.1967+1G>A 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

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-gln1382arg (accessed [today's date]).

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