Is BLM p.Ile947fs (c.2839dup) pathogenic?

BLM p.Ile947fs (c.2839dup) is classified Pathogenic in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-14). Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ile947fs (c.2839dup)?

BLM p.Ile947fs (c.2839dup) is associated with hereditary neoplastic syndrome (ClinVar).

BLM p.Ile947fs

c.2839dup · VCV3480855

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BLM
Protein: p.Ile947fs
Coding: c.2839dup
MANE Select: NM_000057
Type: Duplication
Location: chr15:90790662 (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 947: an α-helix; the helicase c-terminal 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

Similar variants

BLM p.Ile947Thr Uncertain significance ★★ ⚠ same residue
BLM p.Ile947Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Ala481fs Pathogenic ★★ same condition
BLM p.Leu107fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu342fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu393fs Pathogenic ★★ same condition
BLM p.Leu394Ter Pathogenic/Likely pathogenic ★★ same condition
BLM p.Lys657fs 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-ile947fs (accessed [today's date]).

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