ABCB11 p.Arg1268=
c.3802C>A · rs555881834 · VCV1109440
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
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 6.5 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 11.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,062 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.00041%
6/1,461,716 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,212 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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.Arg1268=
- Coding
- c.3802C>A
- MANE Select
- NM_003742
- dbSNP
- rs555881834
- Type
- single nucleotide variant
- Location
- chr2:168923786 (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 1268
- a β-strand; the abc transporter 2 domain; a UniProt-annotated variant site (in pfic2)
Similar variants
- ABCB11 p.Arg1268Gln Pathogenic/Likely pathogenic ★★ same residue
- ABCB11 p.Arg1268Trp Pathogenic/Likely pathogenic ★★ same residue
- ABCB11 p.Arg1268Pro Likely pathogenic ★ same residue
- 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
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-arg1268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown