Is BAG3 p.Arg309Ter (c.925C>T) pathogenic?

BAG3 p.Arg309Ter (c.925C>T) is classified Pathogenic in BAG3 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-05-19). Very rare (popmax 0.0011%, sas); Associated with myofibrillar myopathy 6.

What condition is associated with BAG3 p.Arg309Ter (c.925C>T)?

BAG3 p.Arg309Ter (c.925C>T) is associated with myofibrillar myopathy 6, myocarditis, dilated cardiomyopathy (ClinVar).

How common is BAG3 p.Arg309Ter (c.925C>T) in the general population?

BAG3 p.Arg309Ter (c.925C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is BAG3-related myofibrillar myopathy inherited?

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

BAG3 p.Arg309Ter

c.925C>T · rs869248137 · VCV228322

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

myofibrillar myopathy 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.3, phastCons 0.99
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,046 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00041% 6/1,461,846 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,046
European (non-Finnish)	0.000424%	236,003

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.Arg309Ter
Coding: c.925C>T
MANE Select: NM_004281
dbSNP: rs869248137
Type: single nucleotide variant
Location: chr10:119676479 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 309: 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: myocarditis dilated cardiomyopathy dilated cardiomyopathy 1HH familial dilated cardiomyopathy

For BAG3-related myofibrillar myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

BAG3 p.Arg309Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
BAG3 p.Arg309Gly Uncertain significance ★ ⚠ same residue
BAG3 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg123Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg473Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg90Ter Pathogenic ★★ same condition
BAG3 p.Gln132Ter Pathogenic ★★ same condition
BAG3 p.Gln135Ter 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-arg309ter (accessed [today's date]).

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