Is BLM p.Gln548Ter (c.1642C>T) pathogenic?

BLM p.Gln548Ter (c.1642C>T) is classified Pathogenic in BLM (ClinVar, Multiple submitters, 35 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0189%, nfe); Associated with BLM-related disorder.

What condition is associated with BLM p.Gln548Ter (c.1642C>T)?

BLM p.Gln548Ter (c.1642C>T) is associated with BLM-related disorder, colorectal cancer, Bloom syndrome (ClinVar).

How common is BLM p.Gln548Ter (c.1642C>T) in the general population?

BLM p.Gln548Ter (c.1642C>T) is ultra-rare (popmax 0.0189%, nfe) (gnomAD).

BLM p.Gln548Ter

c.1642C>T · rs200389141 · VCV127478

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 35 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0189%, nfe)

Conditions

BLM-related disorder

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 7 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.41	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.2	GERP 1.8, phastCons 1
Overall
CADD	34.0	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 0.0189% European (non-Finnish) · 222/1,177,058 alleles

Filtering AF 0.0168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0145% 233/1,606,372 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0189%	5,302
Middle Eastern	0.0167%	6,002
Remaining individualsnot grpmax-eligible	0.0113%	8,874
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,264
Admixed American	0.00171%	58,466
Finnishnot grpmax-eligible	0.00157%	63,884

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.Gln548Ter
Coding: c.1642C>T
MANE Select: NM_000057
dbSNP: rs200389141
Type: single nucleotide variant
Location: chr15:90761015 (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 548: the 'necessary for interaction with spidr' region

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

Disease context

BLM-related disorder

Also linked: colorectal cancer Bloom syndrome hereditary neoplastic syndrome

Similar variants

BLM p.Gln548= Likely benign ★★ same residue
BLM p.Gln548Arg Uncertain significance ⚠ same residue
BLM p.Gln548delinsArgLysArgAsnProAlaGlyArgGlyGlySerArgLeuTer Pathogenic ★ same residue
BLM p.Gln548delinsArgProGlyAlaValAlaHisAlaCysAsnProSerThrLeuGlyGlyArgGlyGlyArgIleThrArgSerGlyAspArgAspHisProGlyTer 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

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-gln548ter (accessed [today's date]).

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