ABCB4 p.Gln1258=
c.3774G>A · VCV4846582
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
Conditions
2
familial intrahepatic cholestasis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.08 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 7.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,078 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000137%
2/1,461,758 alleles · very rare
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.Gln1258=
- Coding
- c.3774G>A
- MANE Select
- NM_000443
- Type
- single nucleotide variant
- Location
- chr7:87402162 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.36 · 4 PDB
- Residue 1258
- the abc transporter 2 domain
Similar variants
- ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same condition
- ABCB4 c.2064+3A>T Likely pathogenic ★★ same condition
- ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCB4 c.2783+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ABCB4 c.286+1G>A Pathogenic ★★ same condition
- ABCB4 c.3081+1G>C Pathogenic ★★ same condition
- ABCB4 c.3486+1G>A 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/abcb4-p-gln1258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown