Is BLM p.Asp362= (c.1086C>T) pathogenic?

BLM p.Asp362= (c.1086C>T) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0195%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Asp362= (c.1086C>T)?

BLM p.Asp362= (c.1086C>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Asp362= (c.1086C>T) in the general population?

BLM p.Asp362= (c.1086C>T) is ultra-rare (popmax 0.0195%, nfe) (gnomAD).

BLM p.Asp362=

c.1086C>T · rs375632163 · VCV236799

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.8	GERP -4.9
Overall
CADD	0.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0195% European (non-Finnish) · 230/1,179,906 alleles

Filtering AF 0.0174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.0149% 241/1,613,530 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0195%	5,130
Middle Eastern	0.0164%	6,084
Admixed American	0.00833%	11,998
Remaining individualsnot grpmax-eligible	0.0048%	20,819
African / African-American	0.00134%	74,898
South Asian	0.0011%	91,068

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.Asp362=
Coding: c.1086C>T
MANE Select: NM_000057
dbSNP: rs375632163
Type: single nucleotide variant
Location: chr15:90754937 (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 362: the 'necessary for interaction with spidr' region; the 'necessary for dimerization and homooligomerization' 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.Asp362Glu Uncertain significance ★ ⚠ same residue
BLM p.Asp362His 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
BLM c.2074+1G>T 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-asp362 (accessed [today's date]).

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