Is BLM p.Tyr865Ter (c.2595T>A) pathogenic?

BLM p.Tyr865Ter (c.2595T>A) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). Absent from gnomAD v4.1; Associated with Bloom syndrome.

What condition is associated with BLM p.Tyr865Ter (c.2595T>A)?

BLM p.Tyr865Ter (c.2595T>A) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Tyr865Ter (c.2595T>A) in the general population?

BLM p.Tyr865Ter (c.2595T>A) is absent from gnomAD v4.1 (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Tyr865Ter

c.2595T>A · rs1060503989 · VCV1396588

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 13 of 22
Splicing
SpliceAI	Δ0.29	acceptor loss, 39 bp away · masked 0 · deltas
Pangolin	Δ0.33	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -6.3	GERP -5.2
Overall
CADD	27.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLM
Protein: p.Tyr865Ter
Coding: c.2595T>A
MANE Select: NM_000057
dbSNP: rs1060503989
Type: single nucleotide variant
Location: chr15:90782861 (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 865: a β-strand

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.Tyr865Cys Uncertain significance ★★ ⚠ same residue
BLM p.Tyr865His Uncertain significance ★★ ⚠ same residue
BLM p.Tyr865Ser Uncertain significance ★★ ⚠ same residue
BLM p.Tyr865= Likely benign ★★ same residue
BLM p.Tyr865fs 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

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-tyr865ter (accessed [today's date]).

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