BLM p.Lys1358=
c.4074G>A · rs546163008 · VCV2913421
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
2
hereditary neoplastic syndrome
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 1.1 | GERP -2, phastCons 0.99 |
| Overall | ||
| CADD | 6.667 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,886 alleles
Overall
0.000124%
2/1,614,068 alleles · very rare
exomes 0/1,461,744 · genomes 2/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,886 |
| European (non-Finnish) | 8.47e-05% | 1,179,952 |
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
- BLM
- Protein
- p.Lys1358=
- Coding
- c.4074G>A
- MANE Select
- NM_000057
- dbSNP
- rs546163008
- Type
- single nucleotide variant
- Location
- chr15:90811404 (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 1358
- the 'disordered' region
Similar variants
- BLM p.Lys1358Asn Uncertain significance ★ ⚠ same residue
- BLM c.1087+1G>A Likely pathogenic ★★ same condition
- BLM c.1088-1G>A Likely pathogenic ★★ same condition
- BLM c.1220+2T>C Likely pathogenic ★★ same condition
- BLM c.1220+2T>G Likely pathogenic ★★ same condition
- BLM c.1882+2T>C Likely pathogenic ★★ same condition
- BLM c.2074+1G>T Likely pathogenic ★★ same condition
- BLM c.2075-1G>A 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-lys1358 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown