Is BAG5 p.Gln73Arg (c.218A>G) pathogenic?

BAG5 p.Gln73Arg (c.218A>G) is classified Uncertain significance in BAG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.1201); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with BAG5 p.Gln73Arg (c.218A>G)?

BAG5 p.Gln73Arg (c.218A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BAG5 p.Gln73Arg (c.218A>G) in the general population?

BAG5 p.Gln73Arg (c.218A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BAG5 p.Gln73Arg (c.218A>G)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

BAG5 p.Gln73Arg

c.218A>G · VCV3475073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -6.99	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 3.5	GERP -1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,340 bp · p 0.11 · regional, not allelic
Overall
CADD	16.66	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

Grpmax group 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000274% 4/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.000169%	590,026

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: BAG5
Protein: p.Gln73Arg
Coding: c.218A>G
MANE Select: NM_001015048
Type: single nucleotide variant
Location: chr14:103560947 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 2 PDB
Residue 73: the bag 1 domain

Full BAG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BAG5 c.-12C>T Uncertain significance ★ same condition
BAG5 c.-28T>G Uncertain significance ★ same condition
BAG5 c.-29+612C>T Uncertain significance ★ same condition
BAG5 c.-29+617C>G Uncertain significance ★ same condition
BAG5 c.-29+636A>C Uncertain significance ★ same condition
BAG5 c.-29+654A>T Uncertain significance ★ same condition
BAG5 c.-29+670C>T Uncertain significance ★ same condition
BAG5 c.-29+693C>T Uncertain significance ★ 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/bag5-p-gln73arg (accessed [today's date]).

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