Is BAG1 p.Arg4Pro (c.11G>C) pathogenic?

BAG1 p.Arg4Pro (c.11G>C) is classified Uncertain significance in BAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.1177); Absent from gnomAD v4.1.

How common is BAG1 p.Arg4Pro (c.11G>C) in the general population?

BAG1 p.Arg4Pro (c.11G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAG1 p.Arg4Pro (c.11G>C)?

AlphaMissense predicts likely benign (score 0.1177) — an in-silico prediction, not a clinical call.

BAG1 p.Arg4Pro

c.11G>C · VCV4645062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1177	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -6.44	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 0.64	GERP -2.7, phastCons 0.34
Regional constraint	o/e 1.02	unconstrained · MANE · 9,452 bp · p 0.63 · regional, not allelic
Overall
CADD	19.11	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: BAG1
Protein: p.Arg4Pro
Coding: c.11G>C
MANE Select: NM_004323
Type: single nucleotide variant
Location: chr9:33264664 (GRCh38)
Gene constraint: LOEUF 1.477 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.89 · 29 PDB
Residue 4: the 'disordered' region

Full BAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAG1 p.Ser304Gly Benign ★★ same type
BAG1 p.Ala110Thr Uncertain significance ★ ⚠ same type
BAG1 p.Ala270Val Uncertain significance ★ ⚠ same type
BAG1 p.Ala280Thr Uncertain significance ★ ⚠ same type
BAG1 p.Ala317Val Uncertain significance ★ ⚠ same type
BAG1 p.Ala49Gly Uncertain significance ★ ⚠ same type
BAG1 p.Ala64Thr Uncertain significance ★ ⚠ same type
BAG1 p.Ala65Val Uncertain significance ★ ⚠ 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/bag1-p-arg4pro (accessed [today's date]).

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