Is BCAT1 p.Glu348Lys (c.1042G>A) pathogenic?

BCAT1 p.Glu348Lys (c.1042G>A) is classified Likely benign in BCAT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-03). AlphaMissense: likely benign (0.0677); Rare (popmax 0.608%, nfe); Associated with BCAT1-related disorder.

What condition is associated with BCAT1 p.Glu348Lys (c.1042G>A)?

BCAT1 p.Glu348Lys (c.1042G>A) is associated with BCAT1-related disorder (ClinVar).

How common is BCAT1 p.Glu348Lys (c.1042G>A) in the general population?

BCAT1 p.Glu348Lys (c.1042G>A) is rare (popmax 0.608%, nfe) (gnomAD).

What do computational predictors say about BCAT1 p.Glu348Lys (c.1042G>A)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

BCAT1 p.Glu348Lys

c.1042G>A · rs144632372 · VCV3033269

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.608%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BCAT1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -4.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -2.8, phastCons 0.88
Regional constraint	o/e 0.99	unconstrained · MANE · 131 kb · p 0.77 · regional, not allelic
Overall
CADD	15.84	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 0.608% European (non-Finnish) · 7,145/1,175,170 alleles

Filtering AF 0.596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.591%

Overall 0.514% 8,245/1,603,164 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.608%	164
Remaining individualsnot grpmax-eligible	0.411%	243
Finnishnot grpmax-eligible	0.375%	267
South Asian	0.357%	280
Middle Eastern	0.298%	335
Ashkenazi Jewishnot grpmax-eligible	0.281%	356
Admixed American	0.174%	575
African / African-American	0.115%	869
East Asian	0.00671%	14,908

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.Glu348Lys
Coding: c.1042G>A
MANE Select: NM_005504
dbSNP: rs144632372
Type: single nucleotide variant
Location: chr12:24832725 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.05 · 17 PDB
Residue 348: a β-strand

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

Disease context

BCAT1-related disorder

Similar variants

BCAT1 c.7-72C>T Benign same condition
BCAT1 p.Leu344= Likely benign same condition
BCAT1 p.Ser379= Benign same condition
BCAT1 p.Thr59Met Likely benign ⚠ same condition
BCAT1 p.Tyr374= Likely benign same condition
BCAT1 p.Thr13= Benign ★★ same type
BCAT1 c.7-1070G>A Uncertain significance ★ same type
BCAT1 c.7-1075C>T 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-glu348lys (accessed [today's date]).

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