Is BCAT1 p.Ile284Asn (c.851T>A) pathogenic?

BCAT1 p.Ile284Asn (c.851T>A) is classified Uncertain significance in BCAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: ambiguous (0.3509); Very rare (popmax 0.00966%, nfe).

How common is BCAT1 p.Ile284Asn (c.851T>A) in the general population?

BCAT1 p.Ile284Asn (c.851T>A) is very rare (popmax 0.00966%, nfe) (gnomAD).

What do computational predictors say about BCAT1 p.Ile284Asn (c.851T>A)?

AlphaMissense predicts ambiguous (score 0.3509) — an in-silico prediction, not a clinical call.

BCAT1 p.Ile284Asn

c.851T>A · rs760168308 · VCV2469917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00966%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3509	ambiguous
REVEL	0.318	indeterminate
SaProt	LLR -7.87	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 131 kb · p 0.77 · regional, not allelic
Overall
CADD	26.8	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 0.00966% European (non-Finnish) · 114/1,179,598 alleles

Filtering AF 0.00818% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00719% 116/1,613,004 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00966%	10,347
Remaining individualsnot grpmax-eligible	0.0032%	31,220

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: BCAT1
Protein: p.Ile284Asn
Coding: c.851T>A
MANE Select: NM_005504
dbSNP: rs760168308
Type: single nucleotide variant
Location: chr12:24836563 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.05 · 17 PDB
Residue 284: a β-strand

Full BCAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAT1 p.Thr13= Benign ★★ same type
BCAT1 c.7-1070G>A Uncertain significance ★ same type
BCAT1 c.7-1075C>T Uncertain significance ★ same type
BCAT1 c.7-1078C>T Uncertain significance ★ same type
BCAT1 c.7-1082G>T Uncertain significance ★ same type
BCAT1 c.7-1091C>T Uncertain significance ★ same type
BCAT1 p.Ala27Thr Uncertain significance ★ ⚠ same type
BCAT1 p.Ala298Thr 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/bcat1-p-ile284asn (accessed [today's date]).

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