Is BAG6 p.Arg439Trp (c.1315C>T) pathogenic?

BAG6 p.Arg439Trp (c.1315C>T) is classified Uncertain significance in BAG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.9609); Very rare (popmax 0.00223%, eas).

How common is BAG6 p.Arg439Trp (c.1315C>T) in the general population?

BAG6 p.Arg439Trp (c.1315C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BAG6 p.Arg439Trp (c.1315C>T)?

AlphaMissense predicts likely pathogenic (score 0.9609) — an in-silico prediction, not a clinical call.

BAG6 p.Arg439Trp

c.1315C>T · VCV3985065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9609 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9609	likely pathogenic
REVEL	0.328	indeterminate
SaProt	LLR -11.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.4, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 R445W vs ClinVar R439W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,812 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000481% 7/1,456,152 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,344
East Asiangrpmax	0.00223%	44,812
European (non-Finnish)	0.000425%	235,490

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.Arg439Trp
Coding: c.1315C>T
MANE Select: NM_001387994
Type: single nucleotide variant
Location: chr6:31645000 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.52 · 10 PDB
Residue 439: the '4 x 29 aa approximate repeats' region; the 'disordered' region

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-arg439trp (accessed [today's date]).

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