Is BLM p.Arg899Ter (c.2695C>T) pathogenic?

BLM p.Arg899Ter (c.2695C>T) is classified Pathogenic in BLM (ClinVar, Multiple submitters, 25 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0211%, nfe); Associated with Bloom syndrome.

What condition is associated with BLM p.Arg899Ter (c.2695C>T)?

BLM p.Arg899Ter (c.2695C>T) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Arg899Ter (c.2695C>T) in the general population?

BLM p.Arg899Ter (c.2695C>T) is ultra-rare (popmax 0.0211%, nfe) (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Arg899Ter

c.2695C>T · rs587779884 · VCV127491

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 25 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, nfe)

Conditions

Bloom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 22
Splicing
SpliceAI	Δ0.34	acceptor loss, 32 bp away · masked 0 · deltas
Pangolin	Δ0.34	gain · loss 0.29 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 0.45	GERP -4, phastCons 0.99
Overall
CADD	37.0	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 0.0211% European (non-Finnish) · 249/1,179,986 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0181%

Overall 0.0158% 255/1,613,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0211%	4,739
Remaining individualsnot grpmax-eligible	0.008%	12,497
African / African-American	0.00134%	74,890

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.Arg899Ter
Coding: c.2695C>T
MANE Select: NM_000057
dbSNP: rs587779884
Type: single nucleotide variant
Location: chr15:90784953 (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 899: the '3' overhang dna-binding' region; an α-helix; the helicase c-terminal domain

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

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Arg899Gln Uncertain significance ★★ ⚠ same residue
BLM p.Arg899Gly Uncertain significance ★★ ⚠ same residue
BLM p.Arg899= 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

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-arg899ter (accessed [today's date]).

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