BLM p.Lys498=
c.1494G>A · rs2505426515 · VCV1773853
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Conditions
2
hereditary neoplastic syndrome
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 3.8 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 6.647 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,012 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000205%
3/1,461,780 alleles · very rare
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.Lys498=
- Coding
- c.1494G>A
- MANE Select
- NM_000057
- dbSNP
- rs2505426515
- Type
- single nucleotide variant
- Location
- chr15:90760867 (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 498
- the 'necessary for interaction with spidr' region; a cross-link site
Similar variants
- BLM p.Lys498Ter Pathogenic/Likely pathogenic ★★ same residue
- BLM p.Lys498Arg 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
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-lys498 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown