HBB p.Leu111fs
c.331del · VCV4539279
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 | escapes | premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 6.9 | GERP 1.9, phastCons 0.88 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- HBB
- Protein
- p.Leu111fs
- Coding
- c.331del
- MANE Select
- NM_000518
- Type
- Deletion
- Location
- chr11:5225711 (GRCh38)
- Gene constraint
- LOEUF 1.964 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.09 · 350 PDB
- Residue 111
- a UniProt-annotated variant site (in showa-yakushiji); a functional site ((microbial infection) cleavage; by n.americanus apr-2); an α-helix; the globin domain
Similar variants
- HBB p.Leu111Pro Pathogenic ★★ same residue
- HBB p.Leu111= Conflicting classifications of pathogenicity ★ same residue
- HBB p.Leu111Gln Uncertain significance ★ ⚠ same residue
- HBB c.315+2del Pathogenic/Likely pathogenic ★★ same type
- HBB c.93-22_95del Pathogenic ★★ same type
- HBB c.*110_*111del Pathogenic/Likely pathogenic ★★ same type
- HBB c.*110_*114del Pathogenic/Likely pathogenic ★★ same type
- HBB p.Glu23fs 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/hbb-p-leu111fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown