Is BCAT1 p.Glu356Lys (c.1066G>A) pathogenic?

BCAT1 p.Glu356Lys (c.1066G>A) is classified Uncertain significance in BCAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1295); Ultra-rare (popmax 0.0496%, mid).

How common is BCAT1 p.Glu356Lys (c.1066G>A) in the general population?

BCAT1 p.Glu356Lys (c.1066G>A) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

What do computational predictors say about BCAT1 p.Glu356Lys (c.1066G>A)?

AlphaMissense predicts likely benign (score 0.1295) — an in-silico prediction, not a clinical call.

BCAT1 p.Glu356Lys

c.1066G>A · rs748955974 · VCV2205780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1295 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1295	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 131 kb · p 0.77 · regional, not allelic
Overall
CADD	22.6	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 0.0496% Middle Eastern · 3/6,050 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.000754% 11/1,458,462 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,017
European (non-Finnish)	0.000679%	147,257

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.Glu356Lys
Coding: c.1066G>A
dbSNP: rs748955974
Type: single nucleotide variant
Location: chr12:24829876 (GRCh38)

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

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-glu356lys (accessed [today's date]).

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