Is BLM p.Glu377= (c.1131G>A) pathogenic?

BLM p.Glu377= (c.1131G>A) is classified Likely benign in BLM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-02). Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BLM p.Glu377= (c.1131G>A)?

BLM p.Glu377= (c.1131G>A) is associated with hereditary neoplastic syndrome, Bloom syndrome (ClinVar).

How common is BLM p.Glu377= (c.1131G>A) in the general population?

BLM p.Glu377= (c.1131G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

BLM p.Glu377=

c.1131G>A · rs764842587 · VCV1612323

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -5.6, phastCons 0.001
Overall
CADD	0.435	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,460,364 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
European (non-Finnish)	0.000255%	392,887

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.Glu377=
Coding: c.1131G>A
MANE Select: NM_000057
dbSNP: rs764842587
Type: single nucleotide variant
Location: chr15:90760190 (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 377: 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.Glu377Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BLM p.Glu377fs Pathogenic ★★ 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
BLM c.1882+2T>C Likely pathogenic ★★ same condition
BLM c.2074+1G>T 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-glu377 (accessed [today's date]).

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