Is BLM p.Gln253= (c.759G>A) pathogenic?

BLM p.Gln253= (c.759G>A) is classified Likely benign in BLM (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.084%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Gln253= (c.759G>A)?

BLM p.Gln253= (c.759G>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Gln253= (c.759G>A) in the general population?

BLM p.Gln253= (c.759G>A) is ultra-rare (popmax 0.084%, afr) (gnomAD).

BLM p.Gln253=

c.759G>A · rs34580216 · VCV254781

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.084%, afr)

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 2	GERP -1.4, phastCons 0.99
Overall
CADD	6.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.084% African / African-American · 63/75,032 alleles

Filtering AF 0.0674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0613%

Overall 0.00489% 79/1,614,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.084%	1,191
Admixed American	0.0167%	6,002
Remaining individualsnot grpmax-eligible	0.008%	12,500
East Asian	0.00223%	44,880

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.Gln253=
Coding: c.759G>A
MANE Select: NM_000057
dbSNP: rs34580216
Type: single nucleotide variant
Location: chr15:90750027 (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 253: the 'disordered' 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.Gln253Arg Uncertain significance ★★ ⚠ same residue
BLM p.Gln253Glu Uncertain significance ★★ ⚠ same residue
BLM p.Gln253fs Pathogenic ★ 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-gln253 (accessed [today's date]).

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