Is BLM p.Leu341= (c.1023T>C) pathogenic?

BLM p.Leu341= (c.1023T>C) is classified Likely benign in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-16). Ultra-rare (popmax 0.0156%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Leu341= (c.1023T>C)?

BLM p.Leu341= (c.1023T>C) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Leu341= (c.1023T>C) in the general population?

BLM p.Leu341= (c.1023T>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

BLM p.Leu341=

c.1023T>C · rs28385006 · VCV1767455

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

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 0.21	GERP -2
Overall
CADD	7.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,868 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000434% 7/1,613,960 alleles · ultra-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.Leu341=
Coding: c.1023T>C
MANE Select: NM_000057
dbSNP: rs28385006
Type: single nucleotide variant
Location: chr15:90754874 (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 341: the 'necessary for interaction with spidr' region

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

Also linked: Bloom syndrome

Similar variants

BLM p.Leu341Val Uncertain significance ★★ ⚠ same residue
BLM p.Leu341Ile Uncertain significance ★ ⚠ same residue
BLM p.Leu341Phe 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

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-leu341 (accessed [today's date]).

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