Is ABCC2 p.Ile670Thr (c.2009T>C) pathogenic?

ABCC2 p.Ile670Thr (c.2009T>C) is classified Conflicting classifications of pathogenicity in ABCC2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.1248); Low-frequency (popmax 1.27%, afr); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Ile670Thr (c.2009T>C)?

ABCC2 p.Ile670Thr (c.2009T>C) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Ile670Thr (c.2009T>C) in the general population?

ABCC2 p.Ile670Thr (c.2009T>C) is low-frequency (popmax 1.27%, afr) (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.Ile670Thr (c.2009T>C)?

AlphaMissense predicts likely benign (score 0.1248) — an in-silico prediction, not a clinical call.

ABCC2 p.Ile670Thr

c.2009T>C · rs17222632 · VCV707868

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1248 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.27%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
AlphaMissense	0.1248	likely benign
REVEL	0.49	indeterminate
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	22.8	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 1.27% African / African-American · 954/75,066 alleles

Filtering AF 1.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.0659% 1,064/1,614,018 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.27%	79
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0928%	1,078
Admixed American	0.0533%	1,876
European (non-Finnish)	0.0011%	90,759
South Asian	0.0011%	91,084

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.Ile670Thr
Coding: c.2009T>C
MANE Select: NM_000392
dbSNP: rs17222632
Type: single nucleotide variant
Location: chr10:99813059 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 670: a β-strand; the abc transporter 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-ile670thr (accessed [today's date]).

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