Is BLM p.Ile379= (c.1137C>T) pathogenic?

BLM p.Ile379= (c.1137C>T) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-27). Very rare (popmax 0.00167%, amr); Associated with Bloom syndrome.

What condition is associated with BLM p.Ile379= (c.1137C>T)?

BLM p.Ile379= (c.1137C>T) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Ile379= (c.1137C>T) in the general population?

BLM p.Ile379= (c.1137C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Bloom syndrome inherited?

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

BLM p.Ile379=

c.1137C>T · rs1178783782 · VCV2832291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Bloom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor loss, 45 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP 1.1, phastCons 1
Overall
CADD	7.645	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Overall 0.000124% 2/1,613,020 alleles · very rare exomes 0/1,460,998 · genomes 2/152,022 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
European (non-Finnish)	8.48e-05%	1,179,244

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.Ile379=
Coding: c.1137C>T
MANE Select: NM_000057
dbSNP: rs1178783782
Type: single nucleotide variant
Location: chr15:90760196 (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 379: an α-helix; the 'necessary for interaction with spidr' region; the 'necessary for dimerization and homooligomerization' region

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.Ile379Met Uncertain significance ★★ ⚠ same residue
BLM p.Ile379Ser Uncertain significance ★ ⚠ same residue
BLM p.Ile379Val Uncertain significance ★ ⚠ same residue
BLM p.Ile379Phe 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

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-ile379 (accessed [today's date]).

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