Is BAG1 p.Arg25Trp (c.73C>T) pathogenic?

BAG1 p.Arg25Trp (c.73C>T) is classified Uncertain significance in BAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: ambiguous (0.3687); Ultra-rare (popmax 0.0557%, sas).

How common is BAG1 p.Arg25Trp (c.73C>T) in the general population?

BAG1 p.Arg25Trp (c.73C>T) is ultra-rare (popmax 0.0557%, sas) (gnomAD).

What do computational predictors say about BAG1 p.Arg25Trp (c.73C>T)?

AlphaMissense predicts ambiguous (score 0.3687) — an in-silico prediction, not a clinical call.

BAG1 p.Arg25Trp

c.73C>T · rs772112209 · VCV2393791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3687	ambiguous
REVEL	0.086	moderately benign-leaning
SaProt	LLR -8.78	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 9,452 bp · p 0.63 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0557% South Asian · 33/59,290 alleles

Filtering AF 0.0407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0355%

Overall 0.0045% 62/1,379,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0557%	1,797
Middle Eastern	0.0536%	1,864
Ashkenazi Jewishnot grpmax-eligible	0.0147%	6,788
Remaining individualsnot grpmax-eligible	0.00949%	10,534
Admixed American	0.00375%	26,682
European (non-Finnish)	0.00158%	63,320
African / African-American	0.00153%	65,214

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: BAG1
Protein: p.Arg25Trp
Coding: c.73C>T
MANE Select: NM_004323
dbSNP: rs772112209
Type: single nucleotide variant
Location: chr9:33264602 (GRCh38)
Gene constraint: LOEUF 1.477 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.89 · 29 PDB
Residue 25: the 'disordered' region

Full BAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAG1 p.Ser304Gly Benign ★★ same type
BAG1 p.Ala110Thr Uncertain significance ★ ⚠ same type
BAG1 p.Ala270Val Uncertain significance ★ ⚠ same type
BAG1 p.Ala280Thr Uncertain significance ★ ⚠ same type
BAG1 p.Ala317Val Uncertain significance ★ ⚠ same type
BAG1 p.Ala49Gly Uncertain significance ★ ⚠ same type
BAG1 p.Ala64Thr Uncertain significance ★ ⚠ same type
BAG1 p.Ala65Val 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/bag1-p-arg25trp (accessed [today's date]).

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