Is BAG6 p.Pro435= (c.1305G>A) pathogenic?

BAG6 p.Pro435= (c.1305G>A) is classified Benign in BAG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-11). Common (popmax 5.07%, afr) — too common for a highly-penetrant pathogenic allele.

BAG6 p.Pro435=

Q: How common is BAG6 p.Pro435= (c.1305G>A) in the general population?

BAG6 p.Pro435= (c.1305G>A) is common (popmax 5.07%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1305G>A · rs35843778 · VCV768074

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.07%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -2.8
Overall
CADD	1.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.07% African / African-American · 3,806/75,012 alleles

Filtering AF 4.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.88%

Overall 0.649% 10,461/1,611,390 alleles · common exomes 7,696/1,459,080 · genomes 2,765/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.07%	20
Middle Eastern	2.66%	38
Ashkenazi Jewishnot grpmax-eligible	1.88%	53
Admixed American	1.04%	96
Remaining individualsnot grpmax-eligible	0.964%	104
South Asian	0.903%	111
East Asian	0.35%	286
European (non-Finnish)	0.315%	318
Finnishnot grpmax-eligible	0.0414%	2,416

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.Pro435=
Coding: c.1305G>A
MANE Select: NM_001387994
dbSNP: rs35843778
Type: single nucleotide variant
Location: chr6:31645010 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.52 · 10 PDB
Residue 435: 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.Pro435Ala Uncertain significance ★ ⚠ same residue
BAG6 p.Pro435Leu 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

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-pro435 (accessed [today's date]).

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