HBB p.Pro6=
c.18T>C · rs2133589583 · VCV1620530
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.49e-05%, nfe)
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 0.69 | GERP -0.8 |
| Overall | ||
| CADD | 5.762 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.49e-05%
European (non-Finnish) · 1/1,177,222 alleles
Overall
6.21e-05%
1/1,611,026 alleles · very rare
exomes 1/1,458,720 · genomes 0/152,306 · 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
- HBB
- Protein
- p.Pro6=
- Coding
- c.18T>C
- MANE Select
- NM_000518
- dbSNP
- rs2133589583
- Type
- single nucleotide variant
- Location
- chr11:5227004 (GRCh38)
- Gene constraint
- LOEUF 1.964 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.09 · 350 PDB
- Residue 6
- an α-helix; the globin domain; a UniProt-annotated variant site (in warwickshire)
Similar variants
- HBB p.Pro6Ser Uncertain significance ★★ ⚠ same residue
- HBB p.Pro6Ala Likely benign ★ same residue
- HBB p.Pro6_Glu7delinsSerTer Pathogenic ★ 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
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-pro6 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown