Is BLM p.Thr1243= (c.3729C>T) pathogenic?

BLM p.Thr1243= (c.3729C>T) is classified Likely benign in BLM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-13). Very rare (popmax 0.00439%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Thr1243= (c.3729C>T)?

BLM p.Thr1243= (c.3729C>T) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Thr1243= (c.3729C>T) in the general population?

BLM p.Thr1243= (c.3729C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

BLM p.Thr1243=

c.3729C>T · rs747293738 · VCV236816

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, 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 -9.1	GERP -5.1
Overall
CADD	0.426	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,068 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000991% 16/1,613,916 alleles · very rare exomes 11/1,461,732 · genomes 5/152,184 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,767
Admixed American	0.00333%	30,004
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,912
European (non-Finnish)	0.000678%	147,491

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.Thr1243=
Coding: c.3729C>T
MANE Select: NM_000057
dbSNP: rs747293738
Type: single nucleotide variant
Location: chr15:90804337 (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 1243: the 'necessary for ssdna and dna holliday junction binding' region; an α-helix; the hrdc domain

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.Thr1243Ile Uncertain significance ★★ ⚠ same residue
BLM p.Thr1243fs 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
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-thr1243 (accessed [today's date]).

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