Is BCAT1 p.Cys8Arg (c.22T>C) pathogenic?

BCAT1 p.Cys8Arg (c.22T>C) is classified Uncertain significance in BCAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely benign (0.1163); Very rare (popmax 0.00333%, amr).

How common is BCAT1 p.Cys8Arg (c.22T>C) in the general population?

BCAT1 p.Cys8Arg (c.22T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BCAT1 p.Cys8Arg (c.22T>C)?

AlphaMissense predicts likely benign (score 0.1163) — an in-silico prediction, not a clinical call.

BCAT1 p.Cys8Arg

c.22T>C · VCV3480057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1163 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1163	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -7.85	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 5	GERP 0.32, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 131 kb · p 0.77 · regional, not allelic
Overall
CADD	24.7	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 0.00333% Admixed American · 2/60,032 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000342% 5/1,461,664 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,016
European (non-Finnish)	0.000254%	393,301

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.Cys8Arg
Coding: c.22T>C
MANE Select: NM_005504
Type: single nucleotide variant
Location: chr12:24901870 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.05 · 17 PDB

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-cys8arg (accessed [today's date]).

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