Is BAG3 p.Pro334Leu (c.1001_1002delinsTG) pathogenic?

BAG3 p.Pro334Leu (c.10011002delinsTG) is classified Uncertain significance in BAG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-11). Associated with myofibrillar myopathy 6.

What condition is associated with BAG3 p.Pro334Leu (c.1001_1002delinsTG)?

BAG3 p.Pro334Leu (c.1001_1002delinsTG) is associated with myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How is BAG3-related myofibrillar myopathy inherited?

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

BAG3 p.Pro334Leu

c.1001_1002delinsTG · VCV4788995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

myofibrillar myopathy 6

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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic

Variant & gene context

Gene: BAG3
Protein: p.Pro334Leu
Coding: c.1001_1002delinsTG
MANE Select: NM_004281
Type: Indel
Location: chr10:119676555 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 334: the 'disordered' region

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

Disease context

myofibrillar myopathy 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1HH

For BAG3-related myofibrillar myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

BAG3 p.Glu461Leu Uncertain significance ★★ same condition
BAG3 p.Val432Met Uncertain significance ★★ same condition
BAG3 c.910-21_910-20delinsCG Uncertain significance ★ same condition
BAG3 p.Leu465Met Uncertain significance ★ same condition
BAG3 p.Ser181Asn Uncertain significance ★ same condition
BAG3 p.Trp49Val Uncertain significance ★ same condition
BAG3 c.180+19_180+20delinsTT Likely benign ★ same condition
BAG3 c.910-21_910-20delinsCC Likely benign ★ 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-pro334leu (accessed [today's date]).

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