Is BLM p.Asp219fs (c.656del) pathogenic?

BLM p.Asp219fs (c.656del) is classified Likely pathogenic in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). Associated with Bloom syndrome.

What condition is associated with BLM p.Asp219fs (c.656del)?

BLM p.Asp219fs (c.656del) is associated with Bloom syndrome (ClinVar).

How is Bloom syndrome inherited?

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

BLM p.Asp219fs

c.656del · VCV4063894

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

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 3 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.81	GERP -4.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BLM
Protein: p.Asp219fs
Coding: c.656del
MANE Select: NM_000057
Type: Deletion
Location: chr15:90749924 (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 219: the 'disordered' region

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

For Bloom syndrome (Orphanet):

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

Similar variants

BLM p.Asp219His Uncertain significance ★★ ⚠ same residue
BLM p.Asp219Val Uncertain significance ★★ ⚠ same residue
BLM p.Asp219Ala Uncertain significance ★ ⚠ same residue
BLM p.Asp219Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Asp219Gly 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

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-asp219fs (accessed [today's date]).

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