Is BLM p.Leu1001= (c.3001C>T) pathogenic?

BLM p.Leu1001= (c.3001C>T) is classified Likely benign in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-05). Very rare (popmax 0.00017%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Leu1001= (c.3001C>T)?

BLM p.Leu1001= (c.3001C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Leu1001= (c.3001C>T) in the general population?

BLM p.Leu1001= (c.3001C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

BLM p.Leu1001=

c.3001C>T · VCV4867485

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

hereditary neoplastic 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 5.9	GERP 1.3, phastCons 1
Overall
CADD	11.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,890 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,874 alleles · very rare exomes 1/1,461,688 · genomes 1/152,186 · joint denominator

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.Leu1001=
Coding: c.3001C>T
MANE Select: NM_000057
Type: single nucleotide variant
Location: chr15:90790826 (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 1001: 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BLM p.Leu1001Gln Uncertain significance ★ ⚠ same residue
BLM c.2075-1G>A Likely pathogenic ★★ same condition
BLM c.2193+1G>A Pathogenic/Likely pathogenic ★★ same condition
BLM c.2308-2A>G Pathogenic/Likely pathogenic ★★ same condition
BLM c.2407-2A>G Likely pathogenic ★★ same condition
BLM c.2555+1G>A Likely pathogenic ★★ same condition
BLM c.2556-2A>G Likely pathogenic ★★ same condition
BLM c.2662+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-leu1001 (accessed [today's date]).

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