Is BAG3 p.Pro372fs (c.1115del) pathogenic?

BAG3 p.Pro372fs (c.1115del) is classified Pathogenic/Likely pathogenic in BAG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-19). Very rare (popmax 8.47e-05%, nfe); Associated with dilated cardiomyopathy 1HH.

What condition is associated with BAG3 p.Pro372fs (c.1115del)?

BAG3 p.Pro372fs (c.1115del) is associated with dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Pro372fs (c.1115del) in the general population?

BAG3 p.Pro372fs (c.1115del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

BAG3 p.Pro372fs

c.1115del · VCV4879787

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

dilated cardiomyopathy 1HH

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very rare

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: BAG3
Protein: p.Pro372fs
Coding: c.1115del
MANE Select: NM_004281
Type: Deletion
Location: chr10:119676668 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 372: the 'disordered' region

Full BAG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1HH — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

BAG3 p.Pro372Ser Uncertain significance ★★ ⚠ same residue
BAG3 p.Glu360fs Likely pathogenic ★★ same condition
BAG3 p.Glu471fs Likely pathogenic ★★ same condition
BAG3 p.Gly25fs Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Leu423fs Pathogenic ★★ same condition
BAG3 p.Lys324fs Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Met10fs Pathogenic ★★ same condition
BAG3 p.Pro356fs 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/bag3-p-pro372fs (accessed [today's date]).

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