Is BLM p.Phe1087fs (c.3261del) pathogenic?

BLM p.Phe1087fs (c.3261del) is classified Pathogenic in BLM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-23). Very rare (popmax 0.00136%, nfe); Associated with BLM-related disorder.

What condition is associated with BLM p.Phe1087fs (c.3261del)?

BLM p.Phe1087fs (c.3261del) is associated with BLM-related disorder, Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Phe1087fs (c.3261del) in the general population?

BLM p.Phe1087fs (c.3261del) is very rare (popmax 0.00136%, nfe) (gnomAD).

BLM p.Phe1087fs

c.3261del · rs1319786857 · VCV454132

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

BLM-related disorder

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 17 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.43	GERP -2, phastCons 0.75

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,177,564 alleles

Filtering AF 0.000804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000651%

Overall 0.00117% 17/1,458,688 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00136%	73,598
South Asian	0.0011%	90,936

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.Phe1087fs
Coding: c.3261del
MANE Select: NM_000057
dbSNP: rs1319786857
Type: Deletion
Location: chr15:90798238 (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 1087: an α-helix

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

Disease context

BLM-related disorder

Also linked: Bloom syndrome hereditary neoplastic syndrome

Similar variants

BLM p.Phe1087Cys Uncertain significance ★ ⚠ same residue
BLM p.Phe1087Leu Uncertain significance ★ ⚠ same residue
BLM p.Phe1087= 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-phe1087fs (accessed [today's date]).

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