Is BLM p.Leu107fs (c.320dup) pathogenic?

BLM p.Leu107fs (c.320dup) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-12). Ultra-rare (popmax 0.0245%, eas); Associated with BLM-related disorder.

What condition is associated with BLM p.Leu107fs (c.320dup)?

BLM p.Leu107fs (c.320dup) is associated with BLM-related disorder, hereditary breast ovarian cancer syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Leu107fs (c.320dup) in the general population?

BLM p.Leu107fs (c.320dup) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

BLM p.Leu107fs

c.320dup · rs781221411 · VCV405281

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

BLM-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.5	GERP -5.1
Overall
CADD	18.51	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

Grpmax group 0.0245% East Asian · 11/44,880 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000805% 13/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,080
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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.Leu107fs
Coding: c.320dup
MANE Select: NM_000057
dbSNP: rs781221411
Type: Duplication
Location: chr15:90749586 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 16 PDB

Full BLM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BLM-related disorder

Also linked: hereditary breast ovarian cancer syndrome Bloom syndrome hereditary neoplastic syndrome

Similar variants

BLM p.Leu107Ser Uncertain significance ★ ⚠ same residue
BLM p.Ala481fs Pathogenic ★★ same condition
BLM p.Asp467fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu342fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu393fs Pathogenic ★★ same condition
BLM p.Leu394Ter Pathogenic/Likely pathogenic ★★ same condition
BLM p.Lys657fs Pathogenic ★★ same condition
BLM p.Met348fs 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-leu107fs (accessed [today's date]).

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