Is BAG6 p.Pro694Ser (c.2080C>T) pathogenic?

BAG6 p.Pro694Ser (c.2080C>T) is classified Uncertain significance in BAG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.0819); Very rare (popmax 0.00225%, nfe).

How common is BAG6 p.Pro694Ser (c.2080C>T) in the general population?

BAG6 p.Pro694Ser (c.2080C>T) is very rare (popmax 0.00225%, nfe) (gnomAD).

What do computational predictors say about BAG6 p.Pro694Ser (c.2080C>T)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

BAG6 p.Pro694Ser

c.2080C>T · rs1344493005 · VCV2330257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00225%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.324	indeterminate
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.68, phastCons 1
Overall
CADD	24.1	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P664S vs ClinVar P694S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% European (non-Finnish) · 12/534,268 alleles

Filtering AF 0.0012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000945%

Overall 0.00147% 12/814,244 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: BAG6
Protein: p.Pro694Ser
Coding: c.2080C>T
MANE Select: NM_001387994
dbSNP: rs1344493005
Type: single nucleotide variant
Location: chr6:31642367 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.52 · 10 PDB

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

Similar variants

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
BAG6 p.Arg1150Cys 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-pro694ser (accessed [today's date]).

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