Is BAG6 p.Pro115Thr (c.343C>A) pathogenic?

BAG6 p.Pro115Thr (c.343C>A) is classified Uncertain significance in BAG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: likely benign (0.0602); Very rare (popmax 0.00167%, amr).

How common is BAG6 p.Pro115Thr (c.343C>A) in the general population?

BAG6 p.Pro115Thr (c.343C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BAG6 p.Pro115Thr (c.343C>A)?

AlphaMissense predicts likely benign (score 0.0602) — an in-silico prediction, not a clinical call.

BAG6 p.Pro115Thr

c.343C>A · rs762152993 · VCV3132836

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0602	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.42	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 2.2	GERP 0.54, phastCons 0.99
Overall
CADD	19.47	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 0.00167% Admixed American · 1/60,022 alleles

Overall 0.000274% 4/1,460,888 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,496
South Asian	0.0011%	91,070
European (non-Finnish)	8.47e-05%	1,180,025

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: BAG6
Protein: p.Pro115Thr
Coding: c.343C>A
MANE Select: NM_001387994
dbSNP: rs762152993
Type: single nucleotide variant
Location: chr6:31649279 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.52 · 10 PDB
Residue 115: the 'disordered' region

Full BAG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAG6 p.Pro115Ala Uncertain significance ★ ⚠ same residue
BAG6 p.Gln1137Glu Uncertain significance ★★ ⚠ same type
BAG6 p.Ala1101Val Uncertain significance ★ ⚠ same type
BAG6 p.Ala261Val Uncertain significance ★ ⚠ same type
BAG6 p.Arg1027Trp Uncertain significance ★ ⚠ same type
BAG6 p.Arg1099Trp Uncertain significance ★ ⚠ same type
BAG6 p.Arg1107Gln Uncertain significance ★ ⚠ same type
BAG6 p.Arg1133Gln 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/bag6-p-pro115thr (accessed [today's date]).

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