Is BAG3 p.Arg294Ser (c.880C>A) pathogenic?

BAG3 p.Arg294Ser (c.880C>A) is classified Uncertain significance in BAG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-19). AlphaMissense: ambiguous (0.3852); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with BAG3 p.Arg294Ser (c.880C>A)?

BAG3 p.Arg294Ser (c.880C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is BAG3 p.Arg294Ser (c.880C>A) in the general population?

BAG3 p.Arg294Ser (c.880C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAG3 p.Arg294Ser (c.880C>A)?

AlphaMissense predicts ambiguous (score 0.3852) — an in-silico prediction, not a clinical call.

BAG3 p.Arg294Ser

c.880C>A · rs144585878 · VCV201681

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3852	ambiguous
REVEL	0.272	benign-leaning
SaProt	LLR -8.22	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	23.2	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.Arg294Ser
Coding: c.880C>A
MANE Select: NM_004281
dbSNP: rs144585878
Type: single nucleotide variant
Location: chr10:119672627 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 294: the 'disordered' region

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

Similar variants

BAG3 p.Arg294Cys Uncertain significance ★★ ⚠ same residue
BAG3 p.Arg294His Uncertain significance ★★ ⚠ same residue
BAG3 p.Arg123Ter Pathogenic/Likely 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
BAG3 p.Glu414Ter Pathogenic/Likely 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-arg294ser (accessed [today's date]).

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