ABCB4 p.Asp459=
c.1377T>C · rs150346348 · VCV3014571
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, afr)
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 0.4 | GERP -2.2, phastCons 0.6 |
| Overall | ||
| CADD | 6.797 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
African / African-American · 12/75,052 alleles
Filtering AF
0.0092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0072%
Overall
0.000867%
14/1,614,066 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.016% | 6,254 |
| European (non-Finnish) | 0.000169% | 589,974 |
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.Asp459=
- Coding
- c.1377T>C
- MANE Select
- NM_000443
- dbSNP
- rs150346348
- Type
- single nucleotide variant
- Location
- chr7:87440382 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.36 · 4 PDB
- Residue 459
- the abc transporter 1 domain; a UniProt-annotated variant site (in pfic3; retained in the reticulum endoplasmic; greatly reduced expression)
Similar variants
- ABCB4 p.Asp459Gly Likely pathogenic ★ ⚠ same residue
- ABCB4 p.Asp459His Uncertain significance ★ ⚠ 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-asp459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown