Is BLM p.Ile309del (c.922ATT[1]) pathogenic?

BLM p.Ile309del (c.922ATT[1]) is classified Uncertain significance in BLM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-03). Very rare (popmax 0.00017%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Ile309del (c.922ATT[1])?

BLM p.Ile309del (c.922ATT[1]) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Ile309del (c.922ATT[1]) in the general population?

BLM p.Ile309del (c.922ATT[1]) is very rare (popmax 0.00017%, nfe) (gnomAD).

BLM p.Ile309del

c.922ATT[1] · rs2505400346 · VCV2447179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 · substitutions only
Constraint at this position
Conservation	phyloP 4.3	GERP 1.5, phastCons 0.79

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,176 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,060 alleles · very rare exomes 2/1,460,738 · genomes 0/152,322 · 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.Ile309del
Coding: c.922ATT[1]
MANE Select: NM_000057
dbSNP: rs2505400346
Type: Microsatellite
Location: chr15:90751909 (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 309: the 'necessary for interaction with spidr' region

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.Ile309Val Uncertain significance ★★ ⚠ same residue
BLM p.Ile309Leu Uncertain significance ★ ⚠ same residue
BLM p.Ile309Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Arg191fs Pathogenic ★★ same condition
BLM p.Asn202fs Pathogenic ★★ same condition
BLM p.Asn782fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Cys361_Asp362delinsTer Pathogenic ★★ same condition
BLM p.Gln100fs 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-ile309del (accessed [today's date]).

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