ABCC2 c.1815+4G>A
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.77%, sas)
Conditions
1
Dubin-Johnson syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -1.6 |
| Non-coding constraint | Z 1.18 | 1 kb window · o/e 0.91 · regional · uncalibrated |
| Overall | ||
| CADD | 6.004 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.77%
South Asian · 1,608/91,080 alleles
Filtering AF
1.69%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.66%
Overall
0.104%
1,683/1,613,984 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.77% | 57 |
| Remaining individualsnot grpmax-eligible | 0.102% | 977 |
| Middle Eastern | 0.0165% | 6,060 |
| Admixed American | 0.00333% | 30,005 |
| African / African-American | 0.00133% | 75,002 |
| European (non-Finnish) | 0.000593% | 168,571 |
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
- Coding
- c.1815+4G>A
- MANE Select
- NM_000392
- dbSNP
- rs574319283
- Type
- single nucleotide variant
- Location
- chr10:99808233 (GRCh38)
- Gene constraint
- LOEUF 0.985 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.40 · 16 PDB
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 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-c-1815-plus-4g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown