Is ABCC2 p.Ser1164= (c.3492C>T) pathogenic?

ABCC2 p.Ser1164= (c.3492C>T) is classified Conflicting classifications of pathogenicity in ABCC2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.171%, nfe); Associated with Dubin-Johnson syndrome.

What condition is associated with ABCC2 p.Ser1164= (c.3492C>T)?

ABCC2 p.Ser1164= (c.3492C>T) is associated with Dubin-Johnson syndrome (ClinVar).

How common is ABCC2 p.Ser1164= (c.3492C>T) in the general population?

ABCC2 p.Ser1164= (c.3492C>T) is rare (popmax 0.171%, nfe) (gnomAD).

How is Dubin-Johnson syndrome inherited?

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

ABCC2 p.Ser1164=

c.3492C>T · rs144192700 · VCV298465

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.171%, nfe)

Conditions

Dubin-Johnson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4	GERP -5.5
Overall
CADD	6.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.171% European (non-Finnish) · 2,016/1,180,006 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.162%

Overall 0.154% 2,492/1,614,134 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.81%	17
Finnishnot grpmax-eligible	0.411%	243
European (non-Finnish)grpmax	0.171%	585
Remaining individualsnot grpmax-eligible	0.0992%	1,008
South Asian	0.0648%	1,544
Admixed American	0.0333%	3,001
African / African-American	0.0187%	5,360
Middle Eastern	0.0165%	6,060
East Asian	0.00891%	11,219

Amish 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.Ser1164=
Coding: c.3492C>T
MANE Select: NM_000392
dbSNP: rs144192700
Type: single nucleotide variant
Location: chr10:99836168 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1164: an α-helix; the abc transmembrane type-1 2 domain

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-ser1164 (accessed [today's date]).

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