HBA2 p.Ser85fs
c.254_273del · VCV4818650
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
alpha thalassemia spectrum
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 within the last 50 nt of the penultimate exon (2 of 3, 46 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.12 | |
| Region caveats | ||
| Repeat context | seg dup | · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- HBA2
- Protein
- p.Ser85fs
- Coding
- c.254_273del
- MANE Select
- NM_000517
- Type
- Deletion
- Location
- chr16:173283 (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 85
- a UniProt-annotated variant site (in etobicoke; o(2) affinity up); an α-helix; the globin domain
Similar variants
- HBA2 c.95+2_95+6del Pathogenic ★★★ same condition
- HBA2 c.*93_*94del Pathogenic/Likely pathogenic ★★ same condition
- HBA2 p.Ala116fs Pathogenic/Likely pathogenic ★★ same condition
- HBA2 p.Asp48fs Pathogenic/Likely pathogenic ★★ same condition
- HBA2 p.Gly16fs Likely pathogenic ★★ same condition
- HBA2 p.His21fs Pathogenic ★★ same condition
- HBA2 p.Val108fs Pathogenic/Likely pathogenic ★★ same condition
- HBA2 c.301-12_*57del Likely 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-ser85fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown