Is BLM p.Gln1089= (c.3267A>G) pathogenic?

BLM p.Gln1089= (c.3267A>G) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0165%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Gln1089= (c.3267A>G)?

BLM p.Gln1089= (c.3267A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Gln1089= (c.3267A>G) in the general population?

BLM p.Gln1089= (c.3267A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

BLM p.Gln1089=

c.3267A>G · rs1396484162 · VCV626066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.8, phastCons 1
Overall
CADD	6.902	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,052 alleles

Filtering AF 0.00845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00662%

Overall 0.0011% 16/1,459,342 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,052
South Asian	0.0143%	6,998
Remaining individualsnot grpmax-eligible	0.0016%	62,446
European (non-Finnish)	8.49e-05%	1,178,098

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.Gln1089=
Coding: c.3267A>G
MANE Select: NM_000057
dbSNP: rs1396484162
Type: single nucleotide variant
Location: chr15:90798246 (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 1089: 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.Gln1089Ter Pathogenic ★ same residue
BLM p.Gln1089Glu Uncertain significance ★ ⚠ same residue
BLM p.Gln1089fs Likely pathogenic ★ same residue
BLM c.1087+1G>A Likely pathogenic ★★ same condition
BLM c.1088-1G>A Likely pathogenic ★★ same condition
BLM c.1220+2T>C Likely pathogenic ★★ same condition
BLM c.1220+2T>G Likely pathogenic ★★ same condition
BLM c.1882+2T>C 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-gln1089 (accessed [today's date]).

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