Is BAG3 p.Pro470Ser (c.1408C>T) pathogenic?

BAG3 p.Pro470Ser (c.1408C>T) is classified Pathogenic in BAG3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.975); Absent from gnomAD v4.1; Associated with myofibrillar myopathy 6.

What condition is associated with BAG3 p.Pro470Ser (c.1408C>T)?

BAG3 p.Pro470Ser (c.1408C>T) is associated with myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Pro470Ser (c.1408C>T) in the general population?

BAG3 p.Pro470Ser (c.1408C>T) is absent from gnomAD v4.1 (gnomAD).

How is BAG3-related myofibrillar myopathy inherited?

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

What do computational predictors say about BAG3 p.Pro470Ser (c.1408C>T)?

AlphaMissense predicts likely pathogenic (score 0.975) — an in-silico prediction, not a clinical call.

BAG3 p.Pro470Ser

c.1408C>T · rs756020699 · VCV843736

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

myofibrillar myopathy 6

Computational evidence

Protein change
AlphaMissense	0.975	likely pathogenic ✓ concordant with ClinVar · top 8% in BAG3
REVEL	0.642	indeterminate
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BAG3
Protein: p.Pro470Ser
Coding: c.1408C>T
MANE Select: NM_004281
dbSNP: rs756020699
Type: single nucleotide variant
Location: chr10:119676962 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 470: the bag domain; a UniProt-annotated variant site (in mfm6; likely pathogenic; results in aggregation of chaperones and proteasomal substrates)

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.Pro470= Conflicting classifications of pathogenicity ★ same residue
BAG3 p.Pro470Leu Uncertain significance ★ ⚠ same residue
BAG3 p.Pro470Thr 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

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-pro470ser (accessed [today's date]).

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