Is BAG5 p.Arg390Ter (c.1168C>T) pathogenic?

BAG5 p.Arg390Ter (c.1168C>T) is classified Likely pathogenic in BAG5 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-17). Very rare (popmax 0.00223%, eas); Associated with cardiomyopathy, dilated, 2F.

What condition is associated with BAG5 p.Arg390Ter (c.1168C>T)?

BAG5 p.Arg390Ter (c.1168C>T) is associated with cardiomyopathy, dilated, 2F (ClinVar).

How common is BAG5 p.Arg390Ter (c.1168C>T) in the general population?

BAG5 p.Arg390Ter (c.1168C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

BAG5 p.Arg390Ter

c.1168C>T · rs182208325 · VCV1341488

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

cardiomyopathy, dilated, 2F

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
NMD	escapes	premature termination codon in the last exon (2 of 2) — 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 5.6	GERP 1.7, phastCons 1
Overall
CADD	37.0	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 0.00223% East Asian · 1/44,884 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
European (non-Finnish)	0.000508%	196,671

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: BAG5
Protein: p.Arg390Ter
Coding: c.1168C>T
MANE Select: NM_001015048
dbSNP: rs182208325
Type: single nucleotide variant
Location: chr14:103559997 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 2 PDB
Residue 390: the bag 5 domain; a UniProt-annotated variant site (in cmd2f); a UniProt-annotated variant site (in cmd2f; loss of interaction with hspa8)

Full BAG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiomyopathy, dilated, 2F — 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

BAG5 p.Arg390Gly Uncertain significance ★ ⚠ same residue
BAG5 p.Glu93Gln Uncertain significance ★ ⚠ same condition
BAG5 p.Arg197Ter Pathogenic same condition
BAG5 p.His136fs Likely pathogenic ★ same condition
BAG5 p.His7fs Pathogenic same condition
BAG5 c.-12C>T Uncertain significance ★ same type
BAG5 c.-28T>G Uncertain significance ★ same type
BAG5 c.-29+612C>T Uncertain significance ★ same type

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/bag5-p-arg390ter (accessed [today's date]).

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