ABCB11 p.Arg1226fs
c.3677_3678del · VCV4081073
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function; NMD-escape possible for C-terminal truncations |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ABCB11
- Protein
- p.Arg1226fs
- Coding
- c.3677_3678del
- MANE Select
- NM_003742
- Type
- Deletion
- Location
- chr2:168924744 (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 1226
- an α-helix; the abc transporter 2 domain
Similar variants
- ABCB11 p.Arg1226His Uncertain significance ★★ ⚠ same residue
- ABCB11 p.Arg1226Leu Uncertain significance ★★ ⚠ same residue
- ABCB11 p.Arg1226Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- ABCB11 p.Arg1226Pro Uncertain significance ★ ⚠ same residue
- ABCB11 c.3213+1del Pathogenic ★★ same type
- ABCB11 p.Ala452fs Pathogenic ★★ same type
- ABCB11 p.Arg830fs Pathogenic ★★ same type
- ABCB11 p.Asn199fs 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-arg1226fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown