Is BLM p.Asp297fs (c.890del) pathogenic?

BLM p.Asp297fs (c.890del) is classified Likely pathogenic in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). Very rare (popmax 6.85e-05%); Associated with Bloom syndrome.

What condition is associated with BLM p.Asp297fs (c.890del)?

BLM p.Asp297fs (c.890del) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Asp297fs (c.890del) in the general population?

BLM p.Asp297fs (c.890del) is very rare (popmax 6.85e-05%) (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Asp297fs

c.890del · VCV3578152

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

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 4 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -0.58, phastCons 0.79
Region caveats
Repeat context	tandem	(TGA)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,628 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.Asp297fs
Coding: c.890del
MANE Select: NM_000057
Type: Deletion
Location: chr15:90751877 (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

For Bloom syndrome (Orphanet):

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

Similar variants

BLM p.Asp297Tyr Uncertain significance ★ ⚠ same residue
BLM p.Asp297= 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
BLM p.Arg836fs 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-asp297fs (accessed [today's date]).

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