Is BLM c.3210+2del pathogenic?

BLM c.3210+2del is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00396%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM c.3210+2del?

BLM c.3210+2del is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM c.3210+2del in the general population?

BLM c.3210+2del is very rare (popmax 0.00396%, nfe) (gnomAD).

BLM c.3210+2del

rs587779886 · VCV127497

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00396%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.7	GERP 2.5, phastCons 1
Non-coding constraint	Z 1.00	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	27.9	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 0.00396% European (non-Finnish) · 46/1,162,296 alleles

Filtering AF 0.00303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00271%

Overall 0.00318% 50/1,572,194 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00396%	25,267
Remaining individualsnot grpmax-eligible	0.0033%	30,301
African / African-American	0.00275%	36,397

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
Coding: c.3210+2del
MANE Select: NM_000057
dbSNP: rs587779886
Type: Deletion
Location: chr15:90794359 (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 c.2193+1_2193+9del Pathogenic/Likely pathogenic ★★ same condition
BLM c.3013_3019+4del Likely pathogenic ★★ same condition
BLM c.99-8_112del Pathogenic/Likely pathogenic ★★ same condition
BLM p.Arg545fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Arg836fs Pathogenic ★★ same condition
BLM p.Arg85fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Asn448fs Pathogenic ★★ same condition
BLM p.Asn454fs 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-c-3210-plus-2del (accessed [today's date]).

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