Is BLM p.Arg407Thr (c.1220G>C) pathogenic?

BLM p.Arg407Thr (c.1220G>C) is classified Conflicting classifications of pathogenicity in BLM (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-02). AlphaMissense: likely pathogenic (0.9785); Absent from gnomAD v4.1; Associated with Bloom syndrome.

What condition is associated with BLM p.Arg407Thr (c.1220G>C)?

BLM p.Arg407Thr (c.1220G>C) is associated with Bloom syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BLM p.Arg407Thr (c.1220G>C) in the general population?

BLM p.Arg407Thr (c.1220G>C) is absent from gnomAD v4.1 (gnomAD).

How is Bloom syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BLM p.Arg407Thr (c.1220G>C)?

AlphaMissense predicts likely pathogenic (score 0.9785) — an in-silico prediction, not a clinical call.

BLM p.Arg407Thr

c.1220G>C · rs1350192744 · VCV654963

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9785 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bloom syndrome

Computational evidence

Protein change
AlphaMissense	0.9785	likely pathogenic · top 7% in BLM
REVEL	0.636	indeterminate
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.84	donor loss · deltas
Pangolin	Δ0.73	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 16 kb · p 0.23 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg407Thr
Coding: c.1220G>C
MANE Select: NM_000057
dbSNP: rs1350192744
Type: single nucleotide variant
Location: chr15:90760279 (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

Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Bloom syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BLM p.Arg407Lys Uncertain significance ★★ ⚠ same residue
BLM p.Arg407Ser Uncertain significance ★★ ⚠ same residue
BLM p.Arg407= Likely benign ★★ same residue
BLM p.Arg407Ile Uncertain significance ★ ⚠ 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-arg407thr (accessed [today's date]).

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