HBA2 p.Ala14Pro
c.40G>C · rs281860609 · VCV801175
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000452%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.585 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -8.9 | |
| Regional constraint | o/e 1.06 | unconstrained · MANE · 239 bp · p 0.81 · regional, not allelic |
| Overall | ||
| CADD | 14.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000452%
European (non-Finnish) · 1/221,268 alleles
Overall
0.000268%
1/373,058 alleles · very rare
exomes 1/371,084 · genomes 0/1,974 · 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
- HBA2
- Protein
- p.Ala14Pro
- Coding
- c.40G>C
- MANE Select
- NM_000517
- dbSNP
- rs281860609
- Type
- single nucleotide variant
- Location
- chr16:172952 (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 14
- an α-helix; the globin domain; a UniProt-annotated variant site (in ravenscourt park; causes alpha-thalassemia); a functional site ((microbial infection) cleavage; by n.americanus apr-2)
Similar variants
- HBA2 p.Cys105Arg Likely pathogenic ★★★ same type
- HBA2 p.Leu126Arg Likely pathogenic ★★★ same type
- HBA2 c.*98T>C Uncertain significance ★★★ same type
- HBA2 c.95+27C>T Benign ★★★ same type
- HBA2 c.-24C>G Benign ★★★ same type
- HBA2 c.*107A>G Benign ★★★ same type
- HBA2 c.300+1G>A Likely pathogenic ★★ same type
- HBA2 c.95+1G>A Pathogenic ★★ 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-ala14pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown