Is BAG3 p.Pro512Ser (c.1534C>T) pathogenic?

BAG3 p.Pro512Ser (c.1534C>T) is classified Likely benign in BAG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). AlphaMissense: likely benign (0.1243); Rare (popmax 0.148%, sas); Associated with myofibrillar myopathy 6.

What condition is associated with BAG3 p.Pro512Ser (c.1534C>T)?

BAG3 p.Pro512Ser (c.1534C>T) is associated with myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Pro512Ser (c.1534C>T) in the general population?

BAG3 p.Pro512Ser (c.1534C>T) is rare (popmax 0.148%, sas) (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.Pro512Ser (c.1534C>T)?

AlphaMissense predicts likely benign (score 0.1243) — an in-silico prediction, not a clinical call.

BAG3 p.Pro512Ser

c.1534C>T · rs770086669 · VCV706091

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1243 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myofibrillar myopathy 6

Computational evidence

Protein change
AlphaMissense	0.1243	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.148% South Asian · 135/91,084 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.00849% 137/1,614,048 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.148%	675
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Pro512Ser
Coding: c.1534C>T
MANE Select: NM_004281
dbSNP: rs770086669
Type: single nucleotide variant
Location: chr10:119677088 (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: dilated cardiomyopathy 1HH

For BAG3-related myofibrillar myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

BAG3 p.Pro512= Likely benign ★★ 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-pro512ser (accessed [today's date]).

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