Is BLM p.Lys839del (c.2515_2517del) pathogenic?

BLM p.Lys839del (c.25152517del) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-30). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Lys839del (c.2515_2517del)?

BLM p.Lys839del (c.2515_2517del) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Lys839del (c.2515_2517del) in the general population?

BLM p.Lys839del (c.2515_2517del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

BLM p.Lys839del

c.2515_2517del · rs1190508526 · VCV1792452

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hereditary neoplastic 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 7.6	GERP 2.6, phastCons 1
Overall
CADD	17.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,956 alleles

Overall 0.000124% 2/1,613,912 alleles · very rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
European (non-Finnish)grpmax	8.47e-05%	1,179,956

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys839del
Coding: c.2515_2517del
MANE Select: NM_000057
dbSNP: rs1190508526
Type: Deletion
Location: chr15:90769544 (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 839: the helicase atp-binding domain; an α-helix

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

Disease context

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

Also linked: Bloom syndrome

Similar variants

BLM p.Lys839fs Likely pathogenic ★ same residue
BLM p.Lys839Arg Uncertain significance ★★ ⚠ same residue
BLM p.Lys839Thr Uncertain significance ★★ ⚠ same residue
BLM p.Lys839= Likely benign ★★ same residue
BLM p.Lys839Glu Conflicting classifications of pathogenicity ★ ⚠ 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

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-lys839del (accessed [today's date]).

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