Is BAG3 p.Pro470= (c.1410C>T) pathogenic?

BAG3 p.Pro470= (c.1410C>T) is classified Conflicting classifications of pathogenicity in BAG3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-10-27). Very rare (popmax 0.0011%, sas); Associated with Cardiovascular phenotype.

What condition is associated with BAG3 p.Pro470= (c.1410C>T)?

BAG3 p.Pro470= (c.1410C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Pro470= (c.1410C>T) in the general population?

BAG3 p.Pro470= (c.1410C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

BAG3 p.Pro470=

c.1410C>T · rs749034517 · VCV416022

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Cardiovascular phenotype

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 -11	GERP -4.9
Overall
CADD	1.724	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,064 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000889% 13/1,461,758 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,064
European (non-Finnish)	0.00102%	98,332

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.Pro470=
Coding: c.1410C>T
MANE Select: NM_004281
dbSNP: rs749034517
Type: single nucleotide variant
Location: chr10:119676964 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 6 dilated cardiomyopathy 1HH

Similar variants

BAG3 p.Pro470Ser Pathogenic ★★ ⚠ 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-pro470 (accessed [today's date]).

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