HBA2 p.Pro96Arg
c.287C>G · VCV4280315
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
alpha thalassemia spectrum
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.884 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.27 | phastCons 0.019 |
| Regional constraint | o/e 0.31 | constrained · MANE · 176 bp · p 4.3e-10 · regional, not allelic |
| Overall | ||
| CADD | 24.0 | 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
- HBA2
- Protein
- p.Pro96Arg
- Coding
- c.287C>G
- MANE Select
- NM_000517
- Type
- single nucleotide variant
- Location
- chr16:173316 (GRCh38)
- Gene constraint
- LOEUF 1.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 98.04 · 348 PDB
- Residue 96
- a UniProt-annotated variant site (in denmark hill; o(2) affinity up); a UniProt-annotated variant site (in godavari; o(2) affinity up); the globin domain
Similar variants
- HBA2 p.Pro96Leu Uncertain significance ★ same residue
- HBA2 p.Pro96Ser Uncertain significance ★ same residue
- HBA2 p.Cys105Arg Likely pathogenic ★★★ same condition
- HBA2 p.Leu126Arg Likely pathogenic ★★★ same condition
- HBA2 c.-24C>G Benign ★★★ same condition
- HBA2 c.*107A>G Benign ★★★ same condition
- HBA2 c.300+1G>A Likely pathogenic ★★ same condition
- HBA2 c.95+1G>A 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/hba2-p-pro96arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown