Is BLM p.Leu1173= (c.3519C>T) pathogenic?

BLM p.Leu1173= (c.3519C>T) is classified Likely benign in BLM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-30). Ultra-rare (popmax 0.0164%, mid); Associated with Bloom syndrome.

What condition is associated with BLM p.Leu1173= (c.3519C>T)?

BLM p.Leu1173= (c.3519C>T) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Leu1173= (c.3519C>T) in the general population?

BLM p.Leu1173= (c.3519C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Leu1173=

c.3519C>T · rs769119431 · VCV1153164

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Bloom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.4	GERP -4.8
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000929% 15/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00401%	24,947
Finnishnot grpmax-eligible	0.00156%	63,984
European (non-Finnish)	0.000847%	117,998

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.Leu1173=
Coding: c.3519C>T
MANE Select: NM_000057
dbSNP: rs769119431
Type: single nucleotide variant
Location: chr15:90803681 (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 1173: 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

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.Leu1173Phe Uncertain significance ★ ⚠ 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
BLM c.2075-1G>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-leu1173 (accessed [today's date]).

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