Is BLM p.Asp566del (c.1683TGA[4]) pathogenic?

BLM p.Asp566del (c.1683TGA[4]) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). Very rare (popmax 0.00184%, amr); Associated with Bloom syndrome.

What condition is associated with BLM p.Asp566del (c.1683TGA[4])?

BLM p.Asp566del (c.1683TGA[4]) is associated with Bloom syndrome (ClinVar).

How common is BLM p.Asp566del (c.1683TGA[4]) in the general population?

BLM p.Asp566del (c.1683TGA[4]) is very rare (popmax 0.00184%, amr) (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BLM p.Asp566del

c.1683TGA[4] · rs768095141 · VCV1415476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00184%, amr)

Conditions

Bloom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Region caveats
Repeat context	tandem	(ATGATG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00184% Admixed American · 1/54,328 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000378% 6/1,586,880 alleles · very rare exomes 6/1,434,610 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00184%	54,328
Finnishnot grpmax-eligible	0.00158%	63,096
European (non-Finnish)	0.000342%	292,276

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.Asp566del
Coding: c.1683TGA[4]
MANE Select: NM_000057
dbSNP: rs768095141
Type: Microsatellite
Location: chr15:90761056 (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 566: the 'necessary for interaction with spidr' region

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

Disease context

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

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Asp566dup Uncertain significance ★★ same residue
BLM p.Asp566Asn Uncertain significance ★ ⚠ 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.Gln100fs Pathogenic/Likely 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-asp566del (accessed [today's date]).

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