Is BLM p.Arg959Ter (c.2875C>T) pathogenic?

BLM p.Arg959Ter (c.2875C>T) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-25). Very rare (popmax 0.00223%, eas); Associated with BLM-related disorder.

What condition is associated with BLM p.Arg959Ter (c.2875C>T)?

BLM p.Arg959Ter (c.2875C>T) is associated with BLM-related disorder, Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Arg959Ter (c.2875C>T) in the general population?

BLM p.Arg959Ter (c.2875C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

BLM p.Arg959Ter

c.2875C>T · rs762354041 · VCV405266

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 15 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -1.4, phastCons 1
Overall
CADD	40.0	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,614,118 alleles · very rare exomes 6/1,461,854 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
South Asian	0.0011%	91,076
European (non-Finnish)	0.000339%	295,000

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.Arg959Ter
Coding: c.2875C>T
MANE Select: NM_000057
dbSNP: rs762354041
Type: single nucleotide variant
Location: chr15:90790700 (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 959: the helicase c-terminal domain

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.Arg959Gln Uncertain significance ★★ ⚠ same residue
BLM p.Arg959= Likely benign ★ 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
BLM c.2074+1G>T 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-arg959ter (accessed [today's date]).

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