HBB p.Arg105=
c.315G>A · rs33914944 · VCV1704504
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP 1, phastCons 0.87 |
| Overall | ||
| CADD | 17.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,068 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000372%
6/1,613,910 alleles · very rare
exomes 6/1,461,736 · genomes 0/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,214 |
| European (non-Finnish) | 8.48e-05% | 1,179,888 |
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
- HBB
- Protein
- p.Arg105=
- Coding
- c.315G>A
- MANE Select
- NM_000518
- dbSNP
- rs33914944
- Type
- single nucleotide variant
- Location
- chr11:5226577 (GRCh38)
- Gene constraint
- LOEUF 1.964 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.09 · 350 PDB
- Residue 105
- a UniProt-annotated variant site (in camperdown and duino; associated in cis with p-92 in duino; unstable); a UniProt-annotated variant site (in sherwood forest); a functional site ((microbial infection) cleavage; by n.americanus apr-2); an α-helix; the globin domain
Similar variants
- HBB p.Arg105Ser Uncertain significance ★★ ⚠ same residue
- HBB c.316-146T>G Pathogenic ★★★ same type
- HBB c.316-197C>T Pathogenic ★★★ same type
- HBB c.92+5G>C Pathogenic ★★★ same type
- HBB c.-78A>C Pathogenic ★★★ same type
- HBB c.*111A>G Pathogenic ★★★ same type
- HBB p.Ala28Ser Pathogenic ★★★ ⚠ same type
- HBB p.Lys18Ter 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/hbb-p-arg105 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown