Is BLM p.Leu574= (c.1722A>G) pathogenic?

BLM p.Leu574= (c.1722A>G) is classified Benign/Likely benign in BLM (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.44%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Leu574= (c.1722A>G)?

BLM p.Leu574= (c.1722A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Leu574= (c.1722A>G) in the general population?

BLM p.Leu574= (c.1722A>G) is low-frequency (popmax 2.44%, sas) (gnomAD).

BLM p.Leu574=

c.1722A>G · rs28385011 · VCV136511

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.44%, sas)

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 1.8	GERP -2.1, phastCons 0.86
Overall
CADD	6.862	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.44% South Asian · 1,922/78,694 alleles

Filtering AF 2.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.31%

Overall 0.609% 9,450/1,550,562 alleles · low-frequency exomes 8,769/1,398,274 · genomes 681/152,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.44%	41
Ashkenazi Jewishnot grpmax-eligible	0.93%	108
Middle Eastern	0.734%	136
Remaining individualsnot grpmax-eligible	0.581%	172
European (non-Finnish)	0.557%	179
Finnishnot grpmax-eligible	0.466%	215
Admixed American	0.248%	404
African / African-American	0.0925%	1,082
East Asian	0.0045%	22,220

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.Leu574=
Coding: c.1722A>G
MANE Select: NM_000057
dbSNP: rs28385011
Type: single nucleotide variant
Location: chr15:90761095 (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 574: the 'necessary for interaction with spidr' 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 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
BLM c.2074+1G>T Likely pathogenic ★★ same condition
BLM c.2075-1G>A Likely pathogenic ★★ same condition
BLM c.2193+1G>A 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-leu574 (accessed [today's date]).

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