Is BLM p.Gln1040Ter (c.3118C>T) pathogenic?

BLM p.Gln1040Ter (c.3118C>T) is classified Pathogenic in BLM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-15). Very rare (popmax 8.51e-05%, nfe); Associated with Bloom syndrome.

What condition is associated with BLM p.Gln1040Ter (c.3118C>T)?

BLM p.Gln1040Ter (c.3118C>T) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Gln1040Ter (c.3118C>T) in the general population?

BLM p.Gln1040Ter (c.3118C>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Gln1040Ter

c.3118C>T · rs2151187323 · VCV2137743

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

Bloom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,736 alleles

Overall 6.87e-05% 1/1,454,594 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.Gln1040Ter
Coding: c.3118C>T
MANE Select: NM_000057
dbSNP: rs2151187323
Type: single nucleotide variant
Location: chr15:90794265 (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 1040: an α-helix

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.Gln1040Arg Uncertain significance ★★ ⚠ same residue
BLM p.Gln1040= Likely benign ★★ same residue
BLM p.Gln1040His Uncertain significance ⚠ 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-gln1040ter (accessed [today's date]).

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