Is BCAT2 p.Leu211Phe (c.631C>T) pathogenic?

BCAT2 p.Leu211Phe (c.631C>T) is classified Uncertain significance in BCAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-04). AlphaMissense: likely pathogenic (0.7947); Very rare (popmax 0.00134%, afr).

How common is BCAT2 p.Leu211Phe (c.631C>T) in the general population?

BCAT2 p.Leu211Phe (c.631C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about BCAT2 p.Leu211Phe (c.631C>T)?

AlphaMissense predicts likely pathogenic (score 0.7947) — an in-silico prediction, not a clinical call.

BCAT2 p.Leu211Phe

c.631C>T · VCV4645432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7947	likely pathogenic
REVEL	0.318	indeterminate
SaProt	LLR -15.37	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 9.4	GERP 1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,718 alleles

Overall 0.000126% 2/1,589,426 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,718
European (non-Finnish)	8.55e-05%	1,169,143

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.Leu211Phe
Coding: c.631C>T
MANE Select: NM_001190
Type: single nucleotide variant
Location: chr19:48799739 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 211: a UniProt-annotated variant site (in hvli); a β-strand

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

Similar variants

BCAT2 p.Leu211Val Uncertain significance ★ ⚠ same residue
BCAT2 p.Ala188Thr Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg133His Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg247Trp Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg325Trp Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg333Gly Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg371His Uncertain significance ★★ ⚠ same type
BCAT2 p.Asp112Asn 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/bcat2-p-leu211phe (accessed [today's date]).

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