Is ABCC2 p.Ser978= (c.2934G>A) pathogenic?

ABCC2 p.Ser978= (c.2934G>A) is classified Benign in ABCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.52%, eas); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Ser978= (c.2934G>A)?

ABCC2 p.Ser978= (c.2934G>A) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Ser978= (c.2934G>A) in the general population?

ABCC2 p.Ser978= (c.2934G>A) is low-frequency (popmax 3.52%, eas) (gnomAD).

How is Dubin-Johnson syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCC2 p.Ser978=

c.2934G>A · rs3740070 · VCV732860

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.52%, eas)

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -5
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.52% East Asian · 1,578/44,878 alleles

Filtering AF 3.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.31%

Overall 0.133% 2,149/1,614,140 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.52%	28
Remaining individualsnot grpmax-eligible	0.133%	753
Ashkenazi Jewishnot grpmax-eligible	0.111%	897
South Asian	0.0648%	1,544
European (non-Finnish)	0.0328%	3,049
Middle Eastern	0.0165%	6,062
African / African-American	0.00667%	15,004
Admixed American	0.005%	20,003

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.Ser978=
Coding: c.2934G>A
MANE Select: NM_000392
dbSNP: rs3740070
Type: single nucleotide variant
Location: chr10:99831661 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 978: an α-helix

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 p.Ser978Leu Uncertain significance ★★ ⚠ same residue
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

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-ser978 (accessed [today's date]).

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