Is BAG6 p.Pro695Arg (c.2084C>G) pathogenic?

BAG6 p.Pro695Arg (c.2084C>G) is classified Uncertain significance in BAG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1928); Ultra-rare (popmax 0.0124%, amr).

How common is BAG6 p.Pro695Arg (c.2084C>G) in the general population?

BAG6 p.Pro695Arg (c.2084C>G) is ultra-rare (popmax 0.0124%, amr) (gnomAD).

What do computational predictors say about BAG6 p.Pro695Arg (c.2084C>G)?

AlphaMissense predicts likely benign (score 0.1928) — an in-silico prediction, not a clinical call.

BAG6 p.Pro695Arg

c.2084C>G · rs1339448999 · VCV3132831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1928	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.7, phastCons 1
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P665R vs ClinVar P695R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0124% Admixed American · 6/48,440 alleles

Filtering AF 0.00534% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.000647% 8/1,236,520 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0124%	8,073
Remaining individualsnot grpmax-eligible	0.00201%	49,740
African / African-American	0.00151%	66,430

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.Pro695Arg
Coding: c.2084C>G
MANE Select: NM_001387994
dbSNP: rs1339448999
Type: single nucleotide variant
Location: chr6:31642363 (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-pro695arg (accessed [today's date]).

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