Is BAG1 p.Ser44Phe (c.131C>T) pathogenic?

BAG1 p.Ser44Phe (c.131C>T) is classified Uncertain significance in BAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.1375); Ultra-rare (popmax 0.0692%, afr).

How common is BAG1 p.Ser44Phe (c.131C>T) in the general population?

BAG1 p.Ser44Phe (c.131C>T) is ultra-rare (popmax 0.0692%, afr) (gnomAD).

What do computational predictors say about BAG1 p.Ser44Phe (c.131C>T)?

AlphaMissense predicts likely benign (score 0.1375) — an in-silico prediction, not a clinical call.

BAG1 p.Ser44Phe

c.131C>T · rs757821182 · VCV2465033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1375 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0692%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1375	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -9.36	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 5.8	GERP -0.37, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 9,452 bp · p 0.63 · regional, not allelic
Overall
CADD	22.0	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 0.0692% African / African-American · 50/72,298 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0484%

Overall 0.00342% 52/1,519,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0692%	1,446
European (non-Finnish)	0.000175%	569,879

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.Ser44Phe
Coding: c.131C>T
MANE Select: NM_004323
dbSNP: rs757821182
Type: single nucleotide variant
Location: chr9:33264544 (GRCh38)
Gene constraint: LOEUF 1.477 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.89 · 29 PDB
Residue 44: 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-ser44phe (accessed [today's date]).

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