Is BLM p.Ser595= (c.1785A>T) pathogenic?

BLM p.Ser595= (c.1785A>T) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-31). Rare (popmax 0.163%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ser595= (c.1785A>T)?

BLM p.Ser595= (c.1785A>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Ser595= (c.1785A>T) in the general population?

BLM p.Ser595= (c.1785A>T) is rare (popmax 0.163%, eas) (gnomAD).

BLM p.Ser595=

c.1785A>T · rs79871543 · VCV454085

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, eas)

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 -0.24	GERP -5.1
Overall
CADD	2.979	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% East Asian · 72/44,292 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.00477% 73/1,530,614 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.163%	615
Remaining individualsnot grpmax-eligible	0.0017%	58,848

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.Ser595=
Coding: c.1785A>T
MANE Select: NM_000057
dbSNP: rs79871543
Type: single nucleotide variant
Location: chr15:90761158 (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 595: 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 p.Ser595Ter Pathogenic ★★ same residue
BLM p.Ser595Leu Uncertain significance ★ ⚠ same residue
BLM p.Ser595Pro Uncertain significance ★ ⚠ 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-ser595 (accessed [today's date]).

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