Is BLM p.Pro702= (c.2106T>A) pathogenic?

BLM p.Pro702= (c.2106T>A) is classified Likely benign in BLM (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-02). Very rare (popmax 0.00329%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Pro702= (c.2106T>A)?

BLM p.Pro702= (c.2106T>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Pro702= (c.2106T>A) in the general population?

BLM p.Pro702= (c.2106T>A) is very rare (popmax 0.00329%, sas) (gnomAD).

BLM p.Pro702=

c.2106T>A · rs529421306 · VCV454093

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, 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 -5.5	GERP -5.5
Overall
CADD	0.558	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00266% 43/1,613,586 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
European (non-Finnish)	0.00322%	31,042
Remaining individualsnot grpmax-eligible	0.0032%	31,236

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.Pro702=
Coding: c.2106T>A
MANE Select: NM_000057
dbSNP: rs529421306
Type: single nucleotide variant
Location: chr15:90765327 (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 702: the helicase atp-binding domain; an α-helix

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.Pro702Leu 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
BLM c.2075-1G>A 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-pro702 (accessed [today's date]).

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