Is BLM p.Tyr699Ter (c.2093_2096dup) pathogenic?

BLM p.Tyr699Ter (c.20932096dup) is classified Pathogenic in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-11). Very rare (popmax 0.000255%, nfe); Associated with Bloom syndrome.

What condition is associated with BLM p.Tyr699Ter (c.2093_2096dup)?

BLM p.Tyr699Ter (c.2093_2096dup) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Tyr699Ter (c.2093_2096dup) in the general population?

BLM p.Tyr699Ter (c.2093_2096dup) is very rare (popmax 0.000255%, nfe) (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Tyr699Ter

c.2093_2096dup · rs753973474 · VCV1377631

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000255%, 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 9 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,178,064 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,459,696 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.Tyr699Ter
Coding: c.2093_2096dup
MANE Select: NM_000057
dbSNP: rs753973474
Type: Duplication
Location: chr15:90765313 (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 699: the helicase atp-binding domain; 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.Tyr699Cys Uncertain significance ★★ ⚠ same residue
BLM p.Ala481fs Pathogenic ★★ same condition
BLM p.Asp467fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu107fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu342fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu393fs Pathogenic ★★ same condition
BLM p.Leu394Ter Pathogenic/Likely pathogenic ★★ same condition
BLM p.Lys657fs 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-tyr699ter (accessed [today's date]).

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