Is BAX p.Gly67Arg (c.199G>A) pathogenic?

BAX p.Gly67Arg (c.199G>A) is classified Pathogenic in BAX (ClinVar, No assertion criteria, 1 submitter; last evaluated 1998-04-15). AlphaMissense: likely pathogenic (0.9973); Very rare (popmax 8.49e-05%, nfe); Associated with T-cell acute lymphoblastic leukemia.

What condition is associated with BAX p.Gly67Arg (c.199G>A)?

BAX p.Gly67Arg (c.199G>A) is associated with T-cell acute lymphoblastic leukemia (ClinVar).

How common is BAX p.Gly67Arg (c.199G>A) in the general population?

BAX p.Gly67Arg (c.199G>A) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about BAX p.Gly67Arg (c.199G>A)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

BAX p.Gly67Arg

c.199G>A · rs398122513 · VCV9513

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

T-cell acute lymphoblastic leukemia

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic ✓ concordant with ClinVar · top 6% in BAX
REVEL	0.409	indeterminate
SaProt	LLR -16.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,704 bp · p 0.24 · regional, not allelic
Overall
CADD	28.3	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 8.49e-05% European (non-Finnish) · 1/1,178,482 alleles

Overall 6.85e-05% 1/1,459,188 alleles · very 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: BAX
Protein: p.Gly67Arg
Coding: c.199G>A
MANE Select: NM_138761
dbSNP: rs398122513
Type: single nucleotide variant
Location: chr19:48955799 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.71 · 37 PDB
Residue 67: a UniProt-annotated variant site (in a t-cell acute lymphoblastic leukemia cell line; loss of heterodimerization with bcl-2 or bcl-x(l)); an α-helix

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

Disease context

T-cell acute lymphoblastic leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BAX p.Gly39fs Pathogenic same condition
BAX p.Asp102= Benign ★★ same type
BAX c.474+151G>A Uncertain significance ★ same type
BAX c.474+20C>A Uncertain significance ★ same type
BAX c.474+34C>T Uncertain significance ★ same type
BAX c.474+76G>A Uncertain significance ★ same type
BAX c.474+95G>C Uncertain significance ★ same type
BAX p.Ala81Pro 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/bax-p-gly67arg (accessed [today's date]).

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