HBB p.Ala63=
c.189T>C · rs770878031 · VCV3910010
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -0.49 | GERP -3.7 |
| Overall | ||
| CADD | 6.965 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,866 alleles
Overall
6.2e-05%
1/1,614,094 alleles · very rare
exomes 1/1,461,872 · genomes 0/152,222 · joint denominator
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
- HBB
- Protein
- p.Ala63=
- Coding
- c.189T>C
- MANE Select
- NM_000518
- dbSNP
- rs770878031
- Type
- single nucleotide variant
- Location
- chr11:5226703 (GRCh38)
- Gene constraint
- LOEUF 1.964 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.09 · 350 PDB
- Residue 63
- a UniProt-annotated variant site (in j-europa); a UniProt-annotated variant site (in duarte; unstable); an α-helix; the globin domain
Similar variants
- 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
- HBB p.Trp38Ter 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-ala63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown