ABCB4 p.Thr593=
c.1779G>A · rs143617209 · VCV2989120
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, 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 -6 | GERP -3.7 |
| Overall | ||
| CADD | 3.974 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,882 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000752%
11/1,461,814 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,441 |
| European (non-Finnish) | 0.000763% | 131,108 |
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
- ABCB4
- Protein
- p.Thr593=
- Coding
- c.1779G>A
- MANE Select
- NM_000443
- dbSNP
- rs143617209
- Type
- single nucleotide variant
- Location
- chr7:87431518 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.36 · 4 PDB
- Residue 593
- a UniProt-annotated variant site (in pfic3); a UniProt-annotated variant site (in gbd1); the abc transporter 1 domain
Similar variants
- ABCB4 p.Thr593Ala Uncertain significance ★★ ⚠ same residue
- ABCB4 p.Thr593Met Conflicting classifications of pathogenicity ★ ⚠ same residue
- ABCB4 c.1006-2A>C Pathogenic ★★ same type
- ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same type
- ABCB4 c.1560+1G>A Likely pathogenic ★★ same type
- ABCB4 c.2064+3A>T Likely pathogenic ★★ same type
- ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCB4 c.2682+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/abcb4-p-thr593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown