BCAT2 p.Trp254Cys
c.762G>C · rs964084155 · VCV2160215
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9821 | likely pathogenic · top 2% in BCAT2 |
|---|---|---|
| REVEL | 0.564 | indeterminate |
| SaProt | LLR -15.62 | damaging |
| ⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.27 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 5.8 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.92 | unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic |
| Overall | ||
| CADD | 29.8 | 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
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| East Asiangrpmax | 0.00223% | 44,890 |
| Admixed American | 0.00167% | 59,958 |
| African / African-American | 0.00133% | 74,918 |
| European (non-Finnish) | 0.000169% | 590,002 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Trp254Cys
- Coding
- c.762G>C
- MANE Select
- NM_001190
- dbSNP
- rs964084155
- Type
- single nucleotide variant
- Location
- chr19:48797267 (GRCh38)
- Gene constraint
- LOEUF 1.038 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.47 · 30 PDB
- Residue 254
- a UniProt-annotated variant site (in hvli); a β-strand
Similar variants
- BCAT2 p.Trp254Ter Likely pathogenic ★ 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-trp254cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown