Is BCAT2 p.Pro287Leu (c.860C>T) pathogenic?

BCAT2 p.Pro287Leu (c.860C>T) is classified Uncertain significance in BCAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1664); Very rare (popmax 0.00333%, amr).

How common is BCAT2 p.Pro287Leu (c.860C>T) in the general population?

BCAT2 p.Pro287Leu (c.860C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BCAT2 p.Pro287Leu (c.860C>T)?

AlphaMissense predicts likely benign (score 0.1664) — an in-silico prediction, not a clinical call.

BCAT2 p.Pro287Leu

c.860C>T · rs755519492 · VCV1930895

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1664	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -12.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic
Overall
CADD	23.8	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 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000743% 12/1,614,024 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
East Asian	0.00223%	44,894
South Asian	0.0022%	45,541
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000508%	196,672

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.Pro287Leu
Coding: c.860C>T
MANE Select: NM_001190
dbSNP: rs755519492
Type: single nucleotide variant
Location: chr19:48797001 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 287: a UniProt-annotated variant site (in hvli)

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

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BCAT2 p.Arg371His Uncertain significance ★★ ⚠ same type
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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-pro287leu (accessed [today's date]).

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