Is BLM p.Thr738= (c.2214A>G) pathogenic?

BLM p.Thr738= (c.2214A>G) is classified Likely benign in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-14). Absent from gnomAD v4.1; Associated with Bloom syndrome.

What condition is associated with BLM p.Thr738= (c.2214A>G)?

BLM p.Thr738= (c.2214A>G) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Thr738= (c.2214A>G) in the general population?

BLM p.Thr738= (c.2214A>G) is absent from gnomAD v4.1 (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BLM p.Thr738=

c.2214A>G · rs1256871513 · VCV2989139

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Bloom 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 0.34	GERP -4.8, phastCons 0.62
Overall
CADD	7.605	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLM
Protein: p.Thr738=
Coding: c.2214A>G
MANE Select: NM_000057
dbSNP: rs1256871513
Type: single nucleotide variant
Location: chr15:90766930 (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 738: the helicase atp-binding domain

Full BLM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Thr738Ala Uncertain significance ★★ ⚠ same residue
BLM p.Thr738Arg Uncertain significance ★★ ⚠ same residue
BLM p.Thr738Ile Uncertain significance ★★ ⚠ same residue
BLM p.Thr738Ser Uncertain significance ★ ⚠ same residue
BLM p.Thr738delinsIlePro Likely benign ★ same residue
BLM p.Thr738fs Likely benign ★ same residue
BLM p.Thr738Pro Uncertain significance ★ ⚠ same residue
BLM c.1087+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-thr738 (accessed [today's date]).

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