Is BAG5 p.Val245Ala (c.734T>C) pathogenic?

BAG5 p.Val245Ala (c.734T>C) is classified Uncertain significance in BAG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: ambiguous (0.3735); Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BAG5 p.Val245Ala (c.734T>C)?

BAG5 p.Val245Ala (c.734T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BAG5 p.Val245Ala (c.734T>C) in the general population?

BAG5 p.Val245Ala (c.734T>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about BAG5 p.Val245Ala (c.734T>C)?

AlphaMissense predicts ambiguous (score 0.3735) — an in-silico prediction, not a clinical call.

BAG5 p.Val245Ala

c.734T>C · VCV4192390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3735	ambiguous
REVEL	0.636	indeterminate
SaProt	LLR -6.43	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,340 bp · p 0.11 · regional, not allelic
Overall
CADD	24.7	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 0.000509% European (non-Finnish) · 6/1,179,836 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,882 alleles · very rare

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.Val245Ala
Coding: c.734T>C
MANE Select: NM_001015048
Type: single nucleotide variant
Location: chr14:103560431 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 2 PDB
Residue 245: the bag 3 domain; a UniProt-annotated variant site (in cmd2f)

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-val245ala (accessed [today's date]).

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