HMBS p.Pro119=
c.357T>C · VCV3660335
Likely benign
Single submitter
Classification
Likely benign
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 carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.004 | GERP -4.8, phastCons 0.78 |
| Overall | ||
| CADD | 7.854 | 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.Pro119=
- Coding
- c.357T>C
- MANE Select
- NM_000190
- Type
- single nucleotide variant
- Location
- chr11:119090002 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.81 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 90.54 · 11 PDB
- Residue 119
- a UniProt-annotated variant site (in aip)
Similar variants
- 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
- HMBS c.913-1G>C Pathogenic/Likely pathogenic ★★ same type
- HMBS c.913-2A>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/hmbs-p-pro119 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown