Is BAX p.Val121Ala (c.362T>C) pathogenic?

BAX p.Val121Ala (c.362T>C) is classified Uncertain significance in BAX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely pathogenic (0.8446); Very rare (popmax 0.00191%, amr).

How common is BAX p.Val121Ala (c.362T>C) in the general population?

BAX p.Val121Ala (c.362T>C) is very rare (popmax 0.00191%, amr) (gnomAD).

What do computational predictors say about BAX p.Val121Ala (c.362T>C)?

AlphaMissense predicts likely pathogenic (score 0.8446) — an in-silico prediction, not a clinical call.

BAX p.Val121Ala

c.362T>C · VCV4645215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00191%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8446	likely pathogenic
REVEL	0.226	benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,704 bp · p 0.24 · regional, not allelic
Overall
CADD	25.7	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 0.00191% Admixed American · 1/52,390 alleles

Overall 0.000658% 1/152,082 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.Val121Ala
Coding: c.362T>C
MANE Select: NM_138761
Type: single nucleotide variant
Location: chr19:48956326 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.71 · 37 PDB
Residue 121: an α-helix

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

Similar variants

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
BAX p.Arg134Gly 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-val121ala (accessed [today's date]).

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