HBB p.Leu76=
c.228G>A · VCV4069110
Uncertain significance
No assertion criteria
Classification
Uncertain significance
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
beta thalassemia
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 -0.52 | GERP 0.96 |
| Overall | ||
| CADD | 5.145 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HBB
- Protein
- p.Leu76=
- Coding
- c.228G>A
- MANE Select
- NM_000518
- Type
- single nucleotide variant
- Location
- chr11:5226664 (GRCh38)
- Gene constraint
- LOEUF 1.964 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.09 · 350 PDB
- Residue 76
- a UniProt-annotated variant site (in atlanta; unstable); a UniProt-annotated variant site (in pasadena; o(2) affinity up; unstable); a functional site ((microbial infection) cleavage; by n.americanus apr-2); the globin domain
Similar variants
- HBB p.Leu76fs Pathogenic/Likely pathogenic ★★ same residue
- HBB c.316-146T>G Pathogenic ★★★ same condition
- HBB c.316-197C>T Pathogenic ★★★ same condition
- HBB c.92+5G>C Pathogenic ★★★ same condition
- HBB c.-78A>C Pathogenic ★★★ same condition
- HBB c.*111A>G Pathogenic ★★★ same condition
- HBB p.Ala28Ser Pathogenic ★★★ ⚠ same condition
- HBB p.Lys18Ter Pathogenic ★★★ same condition
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-leu76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown