ABCC9 p.Tyr754=
c.2262T>C · rs145561881 · VCV45403
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 11 submitters
gnomAD v4.1
Rare
rare (popmax 0.281%, mid)
Conditions
4
Cardiovascular phenotype
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 · A>C here scores Δ0.44 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.26 | GERP -1.4, phastCons 0.36 |
| Overall | ||
| CADD | 4.886 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.281%
Middle Eastern · 17/6,046 alleles
Filtering AF
0.179%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.147%
Overall
0.0392%
632/1,612,246 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.281% | 356 |
| Remaining individualsnot grpmax-eligible | 0.0673% | 1,487 |
| South Asian | 0.067% | 1,492 |
| Admixed American | 0.0568% | 1,761 |
| European (non-Finnish) | 0.0405% | 2,471 |
| African / African-American | 0.00134% | 74,888 |
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
- ABCC9
- Protein
- p.Tyr754=
- Coding
- c.2262T>C
- MANE Select
- NM_020297
- dbSNP
- rs145561881
- Type
- single nucleotide variant
- Location
- chr12:21863030 (GRCh38)
- Gene constraint
- LOEUF 0.557 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.72
- Residue 754
- the abc transporter 1 domain
Similar variants
- ABCC9 p.Tyr754His Uncertain significance ★ ⚠ same residue
- ABCC9 c.2506-1G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCC9 p.Arg1116Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ABCC9 p.Arg1116His Pathogenic ★★ ⚠ same condition
- ABCC9 p.Arg1154Gln Pathogenic ★★ same condition
- ABCC9 p.Arg1154Trp Pathogenic/Likely pathogenic ★★ same condition
- ABCC9 p.Gln852Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCC9 p.Gly989Glu 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/abcc9-p-tyr754 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown