Is BCAT1 p.Glu321= (c.963G>A) pathogenic?

BCAT1 p.Glu321= (c.963G>A) is classified Likely benign in BCAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-07). Ultra-rare (popmax 0.0117%, amr).

How common is BCAT1 p.Glu321= (c.963G>A) in the general population?

BCAT1 p.Glu321= (c.963G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

BCAT1 p.Glu321=

c.963G>A · rs762733850 · VCV757514

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.015	GERP -3.4, phastCons 0.033
Overall
CADD	4.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,812 alleles

Filtering AF 0.00545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000479% 7/1,459,986 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: BCAT1
Protein: p.Glu321=
Coding: c.963G>A
MANE Select: NM_005504
dbSNP: rs762733850
Type: single nucleotide variant
Location: chr12:24832804 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.05 · 17 PDB
Residue 321: an α-helix; a UniProt-annotated variant site (in)

Full BCAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAT1 p.Thr13= Benign ★★ same type
BCAT1 c.7-1070G>A Uncertain significance ★ same type
BCAT1 c.7-1075C>T Uncertain significance ★ same type
BCAT1 c.7-1078C>T Uncertain significance ★ same type
BCAT1 c.7-1082G>T Uncertain significance ★ same type
BCAT1 c.7-1091C>T Uncertain significance ★ same type
BCAT1 p.Ala27Thr Uncertain significance ★ ⚠ same type
BCAT1 p.Ala298Thr 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/bcat1-p-glu321 (accessed [today's date]).

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