Is BLM p.Arg818Gly (c.2452_2454delinsGGG) pathogenic?

BLM p.Arg818Gly (c.24522454delinsGGG) is classified Uncertain significance in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-05). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Arg818Gly (c.2452_2454delinsGGG)?

BLM p.Arg818Gly (c.2452_2454delinsGGG) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Arg818Gly (c.2452_2454delinsGGG) in the general population?

BLM p.Arg818Gly (c.2452_2454delinsGGG) is absent from gnomAD (gnomAD).

BLM p.Arg818Gly

c.2452_2454delinsGGG · rs587779882 · VCV127486

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 5.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 46 kb · p 0.035 · regional, not allelic

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.Arg818Gly
Coding: c.2452_2454delinsGGG
MANE Select: NM_000057
dbSNP: rs587779882
Type: Indel
Location: chr15:90769483 (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 818: the helicase atp-binding domain; a turn

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.Arg818Cys Uncertain significance ★★ ⚠ same residue
BLM p.Arg818His Uncertain significance ★★ ⚠ same residue
BLM p.Arg818Leu Uncertain significance ★★ ⚠ same residue
BLM p.Arg818= Likely benign ★★ same residue
BLM p.Asn1141fs Pathogenic/Likely pathogenic ★★ same condition
BLM p.Met1190fs Pathogenic/Likely pathogenic ★★ same condition
BLM c.799+4_799+5delinsCA Uncertain significance ★★ same condition
BLM p.Phe561Asp Uncertain significance ★★ 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-arg818gly (accessed [today's date]).

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