Is BCAT2 p.Glu264Lys (c.790G>A) pathogenic?

BCAT2 p.Glu264Lys (c.790G>A) is classified Pathogenic in BCAT2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.957); Ultra-rare (popmax 0.0165%, mid); Associated with hypervalinemia and hyperleucine-isoleucinemia.

What condition is associated with BCAT2 p.Glu264Lys (c.790G>A)?

BCAT2 p.Glu264Lys (c.790G>A) is associated with hypervalinemia and hyperleucine-isoleucinemia (ClinVar).

How common is BCAT2 p.Glu264Lys (c.790G>A) in the general population?

BCAT2 p.Glu264Lys (c.790G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BCAT2 p.Glu264Lys (c.790G>A)?

AlphaMissense predicts likely pathogenic (score 0.957) — an in-silico prediction, not a clinical call.

BCAT2 p.Glu264Lys

c.790G>A · rs767653663 · VCV869185

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.957 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hypervalinemia and hyperleucine-isoleucinemia

Computational evidence

Protein change
AlphaMissense	0.957	likely pathogenic ✓ concordant with ClinVar · top 7% in BCAT2
REVEL	0.629	indeterminate
SaProt	LLR -13.45	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 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic
Overall
CADD	34.0	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00124% 20/1,613,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
South Asian	0.0121%	8,273
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.000593%	168,556

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: BCAT2
Protein: p.Glu264Lys
Coding: c.790G>A
MANE Select: NM_001190
dbSNP: rs767653663
Type: single nucleotide variant
Location: chr19:48797239 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 264: a UniProt-annotated variant site (in hvli); a UniProt-annotated variant site (in hvli; reduced catalytic activity); a β-strand

Full BCAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypervalinemia and hyperleucine-isoleucinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCAT2 p.Trp254Ter Likely pathogenic ★ same condition
BCAT2 p.Tyr200Ter Pathogenic ★ same condition
BCAT2 p.Ala341Thr Uncertain significance ★ ⚠ same condition
BCAT2 p.Val206Leu Uncertain significance ★ ⚠ same condition
BCAT2 p.Arg170Gln Pathogenic ⚠ same condition
BCAT2 p.Val182Gly Pathogenic same condition
BCAT2 p.Leu301fs Pathogenic/Likely pathogenic ★★ same condition
BCAT2 p.Ala11fs Uncertain significance ★ same condition

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/bcat2-p-glu264lys (accessed [today's date]).

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