Is BAG4 p.Pro288Ala (c.862C>G) pathogenic?

BAG4 p.Pro288Ala (c.862C>G) is classified Uncertain significance in BAG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0583); Very rare (popmax 0.00667%, afr).

How common is BAG4 p.Pro288Ala (c.862C>G) in the general population?

BAG4 p.Pro288Ala (c.862C>G) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about BAG4 p.Pro288Ala (c.862C>G)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

BAG4 p.Pro288Ala

c.862C>G · rs771854090 · VCV3132813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.87	GERP -0.35, phastCons 0.07
Regional constraint	o/e 0.78	unconstrained · MANE · 2,740 bp · p 0.00011 · regional, not allelic
Overall
CADD	7.215	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 0.00667% African / African-American · 5/74,926 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000558% 9/1,614,056 alleles · very rare exomes 5/1,461,886 · genomes 4/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,985
South Asian	0.0022%	45,540
European (non-Finnish)	0.000169%	590,023

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.Pro288Ala
Coding: c.862C>G
MANE Select: NM_004874
dbSNP: rs771854090
Type: single nucleotide variant
Location: chr8:38209241 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.41 · 2 PDB
Residue 288: 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-pro288ala (accessed [today's date]).

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