Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.185%, eas)
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 0.005 | GERP -1.4, phastCons 0.84 |
| Overall | ||
| CADD | 6.386 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.185%
East Asian · 83/44,894 alleles
Filtering AF
0.153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.141%
Overall
0.007%
113/1,614,090 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.185% | 541 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,807 |
| South Asian | 0.011% | 9,109 |
| European (non-Finnish) | 0.000593% | 168,579 |
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.Tyr1309=
- Coding
- c.3927C>T
- MANE Select
- NM_000392
- dbSNP
- rs4148401
- Type
- single nucleotide variant
- Location
- chr10:99844405 (GRCh38)
- Gene constraint
- LOEUF 0.985 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.40 · 16 PDB
- Residue 1309
- the abc transporter 2 domain
Similar variants
- ABCC2 p.Tyr1309fs Likely pathogenic ★ same residue
- ABCC2 c.1031+4A>G Pathogenic/Likely pathogenic ★★ same type
- ABCC2 c.1967+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC2 c.1968-1G>C Pathogenic/Likely pathogenic ★★ same type
- ABCC2 c.3258+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC2 c.333+1G>A Likely pathogenic ★★ same type
- ABCC2 c.3414+1G>A Likely pathogenic ★★ same type
- ABCC2 c.3415-1G>A Pathogenic/Likely pathogenic ★★ same type
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-tyr1309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown