BLM p.Leu1229fs
c.3686_3687del · VCV3658973
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Bloom syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 19 of 22 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 1.5, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- BLM
- Protein
- p.Leu1229fs
- Coding
- c.3686_3687del
- MANE Select
- NM_000057
- Type
- Deletion
- Location
- chr15:90804294 (GRCh38)
- Gene constraint
- LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.10 · 16 PDB
- Residue 1229
- the 'necessary for ssdna and dna holliday junction binding' region; an α-helix; the hrdc domain
Disease context
Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Bloom syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Antenatal, Neonatal
- Prevalence
- 1-9 / 100 000 (Specific population)
Similar variants
- BLM p.Leu1229Val Uncertain significance ★★ ⚠ same residue
- BLM c.2193+1_2193+9del Pathogenic/Likely pathogenic ★★ same condition
- BLM c.3013_3019+4del Likely pathogenic ★★ same condition
- BLM c.3210+2del Pathogenic/Likely pathogenic ★★ same condition
- BLM c.99-8_112del Pathogenic/Likely pathogenic ★★ same condition
- BLM p.Arg545fs Pathogenic/Likely pathogenic ★★ same condition
- BLM p.Arg836fs Pathogenic ★★ same condition
- BLM p.Arg85fs Pathogenic/Likely 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/blm-p-leu1229fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown