Is BLM p.Lys130del (c.387_389del) pathogenic?

BLM p.Lys130del (c.387389del) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-21). Rare (popmax 0.224%, sas); Associated with Bloom syndrome.

What condition is associated with BLM p.Lys130del (c.387_389del)?

BLM p.Lys130del (c.387_389del) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Lys130del (c.387_389del) in the general population?

BLM p.Lys130del (c.387_389del) is rare (popmax 0.224%, sas) (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BLM p.Lys130del

c.387_389del · rs587778105 · VCV421741

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.224%, sas)

Conditions

Bloom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.17	GERP -2.3
Overall
CADD	3.783	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.224% South Asian · 204/91,088 alleles

Filtering AF 0.199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.189%

Overall 0.0129% 209/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.224%	447
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00133%	74,948

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.Lys130del
Coding: c.387_389del
MANE Select: NM_000057
dbSNP: rs587778105
Type: Deletion
Location: chr15:90749653 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 16 PDB

Full BLM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Lys130fs Pathogenic ★ same residue
BLM p.Lys130Arg Uncertain significance ★ ⚠ same residue
BLM p.Lys130= Likely benign ★ 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

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-lys130del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown