Is BAG6 p.Pro595Leu (c.1784C>T) pathogenic?

BAG6 p.Pro595Leu (c.1784C>T) is classified Uncertain significance in BAG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely benign (0.1048); Very rare (popmax 0.00539%, nfe).

How common is BAG6 p.Pro595Leu (c.1784C>T) in the general population?

BAG6 p.Pro595Leu (c.1784C>T) is very rare (popmax 0.00539%, nfe) (gnomAD).

What do computational predictors say about BAG6 p.Pro595Leu (c.1784C>T)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

BAG6 p.Pro595Leu

c.1784C>T · rs753529121 · VCV3132830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00539%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -9.11	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 12	GERP 1.4, phastCons 1
Overall
CADD	28.0	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 P565L vs ClinVar P595L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00539% European (non-Finnish) · 63/1,168,510 alleles

Filtering AF 0.00431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00391%

Overall 0.0048% 76/1,581,872 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0242%	4,130
European (non-Finnish)grpmax	0.00539%	18,548
Remaining individualsnot grpmax-eligible	0.00488%	20,501
African / African-American	0.00268%	37,342
Admixed American	0.00184%	54,490

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro595Leu
Coding: c.1784C>T
MANE Select: NM_001387994
dbSNP: rs753529121
Type: single nucleotide variant
Location: chr6:31643088 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.52 · 10 PDB
Residue 595: the 'disordered' region; the '4 x 29 aa approximate repeats' region

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

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BAG6 p.Arg1107Gln Uncertain significance ★ ⚠ same type
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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-pro595leu (accessed [today's date]).

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