HBB p.Arg31=
c.91A>C · rs35684407 · VCV590773
Likely pathogenic
Multiple submitters
Classification
Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
beta thalassemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.41 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.47 | loss · gain 0.20 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 22.7 | 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
- HBB
- Protein
- p.Arg31=
- Coding
- c.91A>C
- MANE Select
- NM_000518
- dbSNP
- rs35684407
- Type
- single nucleotide variant
- Location
- chr11:5226931 (GRCh38)
- Gene constraint
- LOEUF 1.964 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.09 · 350 PDB
- Residue 31
- a UniProt-annotated variant site (in tacoma; unstable); a functional site ((microbial infection) cleavage; by n.americanus apr-2); an α-helix; the globin domain
Similar variants
- HBB p.Arg31Gly Pathogenic/Likely pathogenic ★★ same residue
- HBB p.Arg31Thr Pathogenic ★★ same residue
- HBB p.Arg31Ser Uncertain significance ★★ ⚠ same residue
- HBB p.Arg31dup Pathogenic same residue
- HBB p.Arg31fs Pathogenic same residue
- HBB p.Arg31Met Likely pathogenic ★ same residue
- HBB c.316-146T>G Pathogenic ★★★ same condition
- HBB c.316-197C>T 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-arg31 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown