Is BCAT2 p.Ile383Phe (c.1147A>T) pathogenic?

BCAT2 p.Ile383Phe (c.1147A>T) is classified Conflicting classifications of pathogenicity in BCAT2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-19). AlphaMissense: likely benign (0.0787); Rare (popmax 0.31%, afr).

How common is BCAT2 p.Ile383Phe (c.1147A>T) in the general population?

BCAT2 p.Ile383Phe (c.1147A>T) is rare (popmax 0.31%, afr) (gnomAD).

What do computational predictors say about BCAT2 p.Ile383Phe (c.1147A>T)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

BCAT2 p.Ile383Phe

c.1147A>T · rs145231743 · VCV2068450

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.31%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.97	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 -0.5	GERP -4.5, phastCons 0.007
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic
Overall
CADD	11.34	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 0.31% African / African-American · 233/75,068 alleles

Filtering AF 0.278% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.265%

Overall 0.0189% 305/1,613,980 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.31%	322
Admixed American	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0192%	5,209
European (non-Finnish)	0.00322%	31,052
South Asian	0.0022%	45,529

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.Ile383Phe
Coding: c.1147A>T
MANE Select: NM_001190
dbSNP: rs145231743
Type: single nucleotide variant
Location: chr19:48795458 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 383: 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.Ile383Val 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-ile383phe (accessed [today's date]).

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