Is BLM p.Gln224Ter (c.670C>T) pathogenic?

BLM p.Gln224Ter (c.670C>T) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-10). Very rare (popmax 0.00534%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Gln224Ter (c.670C>T)?

BLM p.Gln224Ter (c.670C>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Gln224Ter (c.670C>T) in the general population?

BLM p.Gln224Ter (c.670C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

BLM p.Gln224Ter

c.670C>T · rs918752814 · VCV826568

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

hereditary neoplastic 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 3 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.3, phastCons 0.002
Overall
CADD	25.9	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 0.00534% African / African-American · 4/74,926 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,936 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.Gln224Ter
Coding: c.670C>T
MANE Select: NM_000057
dbSNP: rs918752814
Type: single nucleotide variant
Location: chr15:90749938 (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 224: the 'disordered' region

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.Gln224Arg Uncertain significance ★★ ⚠ same residue
BLM p.Gln224His Uncertain significance ★★ ⚠ same residue
BLM p.Gln224Pro Uncertain significance ★★ ⚠ same residue
BLM p.Gln224= Likely benign ★★ same residue
BLM p.Gln224Glu Uncertain significance ★ ⚠ same residue
BLM p.Gln224Lys Uncertain significance ★ ⚠ same residue
BLM c.1087+1G>A Likely pathogenic ★★ same condition
BLM c.1088-1G>A 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-gln224ter (accessed [today's date]).

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