Is BCAT1 p.Leu183Phe (c.547C>T) pathogenic?

BCAT1 p.Leu183Phe (c.547C>T) is classified Uncertain significance in BCAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.3016); Ultra-rare (popmax 0.0343%, nfe).

How common is BCAT1 p.Leu183Phe (c.547C>T) in the general population?

BCAT1 p.Leu183Phe (c.547C>T) is ultra-rare (popmax 0.0343%, nfe) (gnomAD).

What do computational predictors say about BCAT1 p.Leu183Phe (c.547C>T)?

AlphaMissense predicts likely benign (score 0.3016) — an in-silico prediction, not a clinical call.

BCAT1 p.Leu183Phe

c.547C>T · rs200941618 · VCV2458293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0343%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3016	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.11, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 131 kb · p 0.77 · regional, not allelic
Overall
CADD	22.5	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 0.0343% European (non-Finnish) · 405/1,179,146 alleles

Filtering AF 0.0316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0305%

Overall 0.0265% 427/1,612,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0343%	2,911
Remaining individualsnot grpmax-eligible	0.0304%	3,286
Admixed American	0.00167%	59,976
Finnishnot grpmax-eligible	0.00156%	64,004
African / African-American	0.00133%	74,928

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.Leu183Phe
Coding: c.547C>T
MANE Select: NM_005504
dbSNP: rs200941618
Type: single nucleotide variant
Location: chr12:24849913 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.05 · 17 PDB
Residue 183: 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-leu183phe (accessed [today's date]).

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