Computational evidence
| Protein change | ||
| AlphaMissense | 0.1398 | likely benign |
|---|---|---|
| REVEL | 0.765 | pathogenic-leaning |
| SaProt | LLR -9.31 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic |
| Overall | ||
| CADD | 25.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Amishnot grpmax-eligible | 0.329% | 304 |
| European (non-Finnish)grpmax | 0.0508% | 1,967 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,906 |
| Finnishnot grpmax-eligible | 0.025% | 4,002 |
| South Asian | 0.0198% | 5,060 |
| Middle Eastern | 0.0164% | 6,084 |
| African / African-American | 0.00668% | 14,978 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| Admixed American | 0.00167% | 60,000 |
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.Arg1181Gln
- Coding
- c.3542G>A
- MANE Select
- NM_000392
- dbSNP
- rs8187692
- Type
- single nucleotide variant
- Location
- chr10:99836218 (GRCh38)
- Gene constraint
- LOEUF 0.985 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.40 · 16 PDB
- Residue 1181
- an α-helix; the abc transmembrane type-1 2 domain; a UniProt-annotated variant site (decreased expression)
Disease context
Dubin-Johnson syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Dubin-Johnson syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult
Similar variants
- ABCC2 p.Arg1181Ter Pathogenic ★★ same residue
- ABCC2 p.Arg1181Leu Benign/Likely benign ★★ ⚠ 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
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-arg1181gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown