Is BLM p.Arg407= (c.1221A>G) pathogenic?

BLM p.Arg407= (c.1221A>G) is classified Likely benign in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-06). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Arg407= (c.1221A>G)?

BLM p.Arg407= (c.1221A>G) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Arg407= (c.1221A>G) in the general population?

BLM p.Arg407= (c.1221A>G) is absent from gnomAD v4.1 (gnomAD).

BLM p.Arg407=

c.1221A>G · rs900060314 · VCV961916

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.33	acceptor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.6	GERP 0.34, phastCons 1
Overall
CADD	9.378	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLM
Protein: p.Arg407=
Coding: c.1221A>G
MANE Select: NM_000057
dbSNP: rs900060314
Type: single nucleotide variant
Location: chr15:90760594 (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 407: an α-helix; the 'necessary for interaction with spidr' region; the 'necessary for dimerization and homooligomerization' 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

Also linked: Bloom syndrome

Similar variants

BLM p.Arg407Lys Uncertain significance ★★ ⚠ same residue
BLM p.Arg407Ser Uncertain significance ★★ ⚠ same residue
BLM p.Arg407Ile Uncertain significance ★ ⚠ same residue
BLM p.Arg407Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM c.1087+1G>A Likely pathogenic ★★ same condition
BLM c.1088-1G>A Likely pathogenic ★★ same condition
BLM c.1220+2T>C Likely pathogenic ★★ same condition
BLM c.1220+2T>G 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-arg407 (accessed [today's date]).

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