Is BLM p.Gln100fs (c.298_299del) pathogenic?

BLM p.Gln100fs (c.298299del) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-17). Very rare (popmax 0.00333%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Gln100fs (c.298_299del)?

BLM p.Gln100fs (c.298_299del) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Gln100fs (c.298_299del) in the general population?

BLM p.Gln100fs (c.298_299del) is very rare (popmax 0.00333%, amr) (gnomAD).

BLM p.Gln100fs

c.298_299del · rs745807085 · VCV371569

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

hereditary neoplastic syndrome

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 -0.82	GERP -4.3
Overall
CADD	18.3	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 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000743% 12/1,614,068 alleles · very rare exomes 10/1,461,856 · genomes 2/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,006
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,918
European (non-Finnish)	0.000678%	147,506

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.Gln100fs
Coding: c.298_299del
MANE Select: NM_000057
dbSNP: rs745807085
Type: Microsatellite
Location: chr15:90749563 (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

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

Also linked: Bloom syndrome

Similar variants

BLM p.Gln100Arg Uncertain significance ★ ⚠ same residue
BLM p.Gln100Pro Uncertain significance ★ ⚠ same residue
BLM p.Gln100= Likely benign ★ same residue
BLM p.Arg191fs Pathogenic ★★ same condition
BLM p.Asn202fs Pathogenic ★★ same condition
BLM p.Asn782fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Cys361_Asp362delinsTer Pathogenic ★★ same condition
BLM p.Gln802fs Pathogenic/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-gln100fs (accessed [today's date]).

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