Is ABCC2 p.Arg1150His (c.3449G>A) pathogenic?

ABCC2 p.Arg1150His (c.3449G>A) is classified Pathogenic/Likely pathogenic in ABCC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-18). AlphaMissense: likely pathogenic (0.6996); Ultra-rare (popmax 0.0167%, mid); Associated with ABCC2-related disorder.

What condition is associated with ABCC2 p.Arg1150His (c.3449G>A)?

ABCC2 p.Arg1150His (c.3449G>A) is associated with ABCC2-related disorder, Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Arg1150His (c.3449G>A) in the general population?

ABCC2 p.Arg1150His (c.3449G>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ABCC2 p.Arg1150His (c.3449G>A)?

AlphaMissense predicts likely pathogenic (score 0.6996) — an in-silico prediction, not a clinical call.

ABCC2 p.Arg1150His

c.3449G>A · rs72558200 · VCV8419

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.6996 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCC2-related disorder

Computational evidence

Protein change
AlphaMissense	0.6996	likely pathogenic ✓ concordant with ClinVar
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -13.16	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 12	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 0.0167% Middle Eastern · 1/5,996 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00787% 127/1,613,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,996
Admixed American	0.0133%	7,499
Remaining individualsnot grpmax-eligible	0.0112%	8,925
European (non-Finnish)	0.0083%	12,041
African / African-American	0.00668%	14,981
South Asian	0.00659%	15,181
East Asian	0.00445%	22,452

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.Arg1150His
Coding: c.3449G>A
MANE Select: NM_000392
dbSNP: rs72558200
Type: single nucleotide variant
Location: chr10:99836125 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1150: an α-helix; the abc transmembrane type-1 2 domain; a UniProt-annotated variant site (in djs; protein is properly localized at the plasma membrane, but transporter activity is impaired)

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.Arg1150Cys 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
ABCC2 c.3741+1G>T 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-arg1150his (accessed [today's date]).

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