Is BAG3 p.Asn215= (c.645C>T) pathogenic?

BAG3 p.Asn215= (c.645C>T) is classified Likely benign in BAG3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0173%, nfe); Associated with myofibrillar myopathy 6.

What condition is associated with BAG3 p.Asn215= (c.645C>T)?

BAG3 p.Asn215= (c.645C>T) is associated with myofibrillar myopathy 6, cardiomyopathy, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Asn215= (c.645C>T) in the general population?

BAG3 p.Asn215= (c.645C>T) is ultra-rare (popmax 0.0173%, nfe) (gnomAD).

How is BAG3-related myofibrillar myopathy inherited?

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

BAG3 p.Asn215=

c.645C>T · rs138078305 · VCV178008

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.6	GERP -4.6
Overall
CADD	1.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% European (non-Finnish) · 204/1,180,030 alleles

Filtering AF 0.0153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0153% 247/1,614,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.05%	2,001
European (non-Finnish)grpmax	0.0173%	5,784
Remaining individualsnot grpmax-eligible	0.0144%	6,943
African / African-American	0.00267%	37,462

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn215=
Coding: c.645C>T
MANE Select: NM_004281
dbSNP: rs138078305
Type: single nucleotide variant
Location: chr10:119672392 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98

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: cardiomyopathy dilated cardiomyopathy 1HH

For BAG3-related myofibrillar myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

BAG3 p.Asn215Lys Uncertain significance ★ ⚠ same residue
BAG3 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg123Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg309Ter 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-asn215 (accessed [today's date]).

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