HBA2 p.Phe44Val
c.130T>G · rs281864829 · VCV2428504
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
thalassemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.95 | strongly pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | phastCons 1 |
| Regional constraint | o/e 0.31 | constrained · MANE · 176 bp · p 4.3e-10 · regional, not allelic |
| Overall | ||
| CADD | 25.1 | 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.Phe44Val
- Coding
- c.130T>G
- MANE Select
- NM_000517
- dbSNP
- rs281864829
- Type
- single nucleotide variant
- Location
- chr16:173159 (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 44
- the globin domain; a UniProt-annotated variant site (in hirosaki; unstable)
Similar variants
- HBA2 p.Phe44Leu Likely pathogenic ★★ same residue
- HBA2 p.Met1Ile Likely pathogenic ★ same condition
- HBA2 p.Phe44fs Likely pathogenic ★ same residue
- HBA2 c.-157C>T Uncertain significance ★ same condition
- HBA2 c.*108G>A Uncertain significance ★ same condition
- HBA2 p.Cys105Arg Likely pathogenic ★★★ same type
- HBA2 p.Leu126Arg Likely pathogenic ★★★ same type
- HBA2 c.*98T>C Uncertain significance ★★★ 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/hba2-p-phe44val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown