Is BLM p.Arg1086fs (c.3254dup) pathogenic?

BLM p.Arg1086fs (c.3254dup) is classified Pathogenic in BLM (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with endometrial carcinoma.

What condition is associated with BLM p.Arg1086fs (c.3254dup)?

BLM p.Arg1086fs (c.3254dup) is associated with endometrial carcinoma, colorectal cancer, hereditary breast carcinoma (ClinVar).

How common is BLM p.Arg1086fs (c.3254dup) in the general population?

BLM p.Arg1086fs (c.3254dup) is no gnomAD frequency available for this variant (gnomAD).

BLM p.Arg1086fs

c.3254dup · rs2505534508 · VCV2499621

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

endometrial carcinoma

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 17 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.13	GERP -4.7, phastCons 0.003

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BLM
Protein: p.Arg1086fs
Coding: c.3254dup
MANE Select: NM_000057
dbSNP: rs2505534508
Type: Duplication
Location: chr15:90798232 (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 1086: an α-helix

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

Disease context

endometrial carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer hereditary breast carcinoma

Similar variants

BLM c.99-8_112del Pathogenic/Likely pathogenic ★★ same condition
BLM p.Gln548Ter Pathogenic ★★ same condition
BLM p.Ala915Val Uncertain significance ★★ ⚠ same condition
BLM p.Phe644Tyr Uncertain significance ★★ ⚠ same condition
BLM p.Thr1015Ile Uncertain significance ★★ ⚠ same condition
BLM p.Thr127Ile Uncertain significance ★★ ⚠ same condition
BLM p.Lys1186Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
BLM p.Lys1200fs 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-arg1086fs (accessed [today's date]).

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