HMBS p.Ala11=
c.33G>C · rs1592208560 · VCV640707
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.36 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.35 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 26.2 | 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
- HMBS
- Protein
- p.Ala11=
- Coding
- c.33G>C
- MANE Select
- NM_000190
- dbSNP
- rs1592208560
- Type
- single nucleotide variant
- Location
- chr11:119085066 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.81 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 90.54 · 11 PDB
Similar variants
- HMBS p.Ala11Val Uncertain significance ★ ⚠ same residue
- HMBS p.Ala11Thr Likely benign ★ same residue
- HMBS c.160+5G>C Pathogenic/Likely pathogenic ★★ same type
- HMBS c.345-1G>A Pathogenic ★★ same type
- HMBS c.613-1G>A Pathogenic ★★ same type
- HMBS c.826-2A>T Pathogenic/Likely pathogenic ★★ same type
- HMBS c.912+2T>C Pathogenic ★★ same type
- HMBS c.913-1G>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/hmbs-p-ala11 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown