Is BLM p.Thr830fs (c.2488dup) pathogenic?

BLM p.Thr830fs (c.2488dup) is classified Pathogenic/Likely pathogenic in BLM (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-21). Very rare (popmax 0.000339%, nfe); Associated with BLM-related disorder.

What condition is associated with BLM p.Thr830fs (c.2488dup)?

BLM p.Thr830fs (c.2488dup) is associated with BLM-related disorder, Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Thr830fs (c.2488dup) in the general population?

BLM p.Thr830fs (c.2488dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

BLM p.Thr830fs

c.2488dup · rs367543019 · VCV42178

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

BLM-related disorder

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 12 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -5.2
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,884 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,874 alleles · very rare exomes 3/1,461,688 · genomes 1/152,186 · joint denominator

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.Thr830fs
Coding: c.2488dup
MANE Select: NM_000057
dbSNP: rs367543019
Type: Duplication
Location: chr15:90769518 (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 830: the helicase atp-binding domain; a β-strand

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

Disease context

BLM-related disorder

Also linked: Bloom syndrome hereditary neoplastic syndrome

Similar variants

BLM p.Thr830Arg Uncertain significance ★★ ⚠ same residue
BLM p.Thr830Lys Uncertain significance ★★ ⚠ same residue
BLM p.Thr830Met Uncertain significance ★★ ⚠ same residue
BLM p.Thr830= Likely benign ★★ same residue
BLM p.Ala481fs Pathogenic ★★ same condition
BLM p.Asp467fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu107fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Leu342fs Pathogenic/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-thr830fs (accessed [today's date]).

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