Is BAG5 p.Thr139Ile (c.416C>T) pathogenic?

BAG5 p.Thr139Ile (c.416C>T) is classified Uncertain significance in BAG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.8524); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BAG5 p.Thr139Ile (c.416C>T)?

BAG5 p.Thr139Ile (c.416C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BAG5 p.Thr139Ile (c.416C>T) in the general population?

BAG5 p.Thr139Ile (c.416C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAG5 p.Thr139Ile (c.416C>T)?

AlphaMissense predicts likely pathogenic (score 0.8524) — an in-silico prediction, not a clinical call.

BAG5 p.Thr139Ile

c.416C>T · VCV4192379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8524 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8524	likely pathogenic · top 8% in BAG5
REVEL	0.498	indeterminate
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,340 bp · p 0.11 · regional, not allelic
Overall
CADD	26.0	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: BAG5
Protein: p.Thr139Ile
Coding: c.416C>T
MANE Select: NM_001015048
Type: single nucleotide variant
Location: chr14:103560749 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 2 PDB
Residue 139: the bag 2 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-thr139ile (accessed [today's date]).

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