Is BCAT2 p.Val206Met (c.616G>A) pathogenic?

BCAT2 p.Val206Met (c.616G>A) is classified Uncertain significance in BCAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely benign (0.0746); Very rare (popmax 8.59e-05%, nfe).

How common is BCAT2 p.Val206Met (c.616G>A) in the general population?

BCAT2 p.Val206Met (c.616G>A) is very rare (popmax 8.59e-05%, nfe) (gnomAD).

What do computational predictors say about BCAT2 p.Val206Met (c.616G>A)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

BCAT2 p.Val206Met

c.616G>A · rs1393183522 · VCV2870532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.59e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -8.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -4
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic
Overall
CADD	0.412	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 8.59e-05% European (non-Finnish) · 1/1,164,266 alleles

Overall 7e-05% 1/1,429,020 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: BCAT2
Protein: p.Val206Met
Coding: c.616G>A
MANE Select: NM_001190
dbSNP: rs1393183522
Type: single nucleotide variant
Location: chr19:48799754 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 206: a UniProt-annotated variant site (in hvli)

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

Similar variants

BCAT2 p.Val206Leu 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-val206met (accessed [today's date]).

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