Is BAG6 p.His307= (c.921C>T) pathogenic?

BAG6 p.His307= (c.921C>T) is classified Likely benign in BAG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-29). Ultra-rare (popmax 0.0267%, eas).

How common is BAG6 p.His307= (c.921C>T) in the general population?

BAG6 p.His307= (c.921C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

BAG6 p.His307=

c.921C>T · rs555713768 · VCV715339

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.92	GERP -3.1
Overall
CADD	7.739	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,886 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.0177% 286/1,612,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0928%	1,077
East Asiangrpmax	0.0267%	3,740
European (non-Finnish)	0.0176%	5,673
Admixed American	0.01%	9,999
African / African-American	0.00133%	75,034
South Asian	0.0011%	91,056

Remaining individuals 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.His307=
Coding: c.921C>T
MANE Select: NM_001387994
dbSNP: rs555713768
Type: single nucleotide variant
Location: chr6:31645602 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.52 · 10 PDB
Residue 307: the '4 x 29 aa approximate repeats' 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-his307 (accessed [today's date]).

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