Is BAG3 p.Pro32Thr (c.94C>A) pathogenic?

BAG3 p.Pro32Thr (c.94C>A) is classified Uncertain significance in BAG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-25). AlphaMissense: likely pathogenic (0.8906); Absent from gnomAD v4.1.

How common is BAG3 p.Pro32Thr (c.94C>A) in the general population?

BAG3 p.Pro32Thr (c.94C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAG3 p.Pro32Thr (c.94C>A)?

AlphaMissense predicts likely pathogenic (score 0.8906) — an in-silico prediction, not a clinical call.

BAG3 p.Pro32Thr

c.94C>A · VCV4687016

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8906 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8906	likely pathogenic
REVEL	0.605	indeterminate
SaProt	LLR -11.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.82, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Pro32Thr
Coding: c.94C>A
MANE Select: NM_004281
Type: single nucleotide variant
Location: chr10:119651769 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 32: the ww 1 domain; the 'disordered' region

Full BAG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAG3 p.Pro32Arg Uncertain significance ★★ ⚠ same residue
BAG3 p.Pro32Leu Uncertain significance ★★ ⚠ same residue
BAG3 p.Pro32= Likely benign ★ same residue
BAG3 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same type
BAG3 p.Arg123Ter Pathogenic/Likely pathogenic ★★ same type
BAG3 p.Arg309Ter Pathogenic ★★ same type
BAG3 p.Arg473Ter Pathogenic/Likely pathogenic ★★ same type
BAG3 p.Arg90Ter Pathogenic ★★ same type

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-pro32thr (accessed [today's date]).

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