ABCB11 p.Ala819=
c.2457C>A · rs1398103963 · VCV502754
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0151%, amr)
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 1.8 | GERP -4.2, phastCons 1 |
| Overall | ||
| CADD | 4.254 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0151%
Admixed American · 9/59,790 alleles
Filtering AF
0.00776%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0058%
Overall
0.000682%
11/1,612,332 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0151% | 6,643 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,187 |
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
- ABCB11
- Protein
- p.Ala819=
- Coding
- c.2457C>A
- MANE Select
- NM_003742
- dbSNP
- rs1398103963
- Type
- single nucleotide variant
- Location
- chr2:168944758 (GRCh38)
- Gene constraint
- LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 83.23 · 9 PDB
- Residue 819
- an α-helix; the abc transmembrane type-1 2 domain
Similar variants
- ABCB11 c.1084-2A>G Pathogenic ★★ same type
- ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.1198-2A>C Likely pathogenic ★★ same type
- ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.150+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.150+2T>C Pathogenic/Likely pathogenic ★★ same type
- ABCB11 c.150+3A>C 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/abcb11-p-ala819 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown