Is BAG4 p.Ser308Cys (c.922A>T) pathogenic?

BAG4 p.Ser308Cys (c.922A>T) is classified Uncertain significance in BAG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.0747); Ultra-rare (popmax 0.0187%, afr).

How common is BAG4 p.Ser308Cys (c.922A>T) in the general population?

BAG4 p.Ser308Cys (c.922A>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about BAG4 p.Ser308Cys (c.922A>T)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

BAG4 p.Ser308Cys

c.922A>T · rs140547293 · VCV2373473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3	GERP -1.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,740 bp · p 0.00011 · regional, not allelic
Overall
CADD	20.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,934 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.000867% 14/1,614,086 alleles · ultra-rare

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: BAG4
Protein: p.Ser308Cys
Coding: c.922A>T
MANE Select: NM_004874
dbSNP: rs140547293
Type: single nucleotide variant
Location: chr8:38210041 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.41 · 2 PDB
Residue 308: the 'disordered' region

Full BAG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAG4 p.Ala107Val Uncertain significance ★ ⚠ same type
BAG4 p.Ala157Val Uncertain significance ★ ⚠ same type
BAG4 p.Ala248Thr Uncertain significance ★ ⚠ same type
BAG4 p.Ala447Val Uncertain significance ★ ⚠ same type
BAG4 p.Arg185His Uncertain significance ★ ⚠ same type
BAG4 p.Arg311Trp Uncertain significance ★ ⚠ same type
BAG4 p.Arg40Leu Uncertain significance ★ ⚠ same type
BAG4 p.Arg51Gln 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/bag4-p-ser308cys (accessed [today's date]).

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