Is BCAT2 p.His46Arg (c.137A>G) pathogenic?

BCAT2 p.His46Arg (c.137A>G) is classified Uncertain significance in BCAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-10). AlphaMissense: likely benign (0.0522); Rare (popmax 0.132%, mid).

How common is BCAT2 p.His46Arg (c.137A>G) in the general population?

BCAT2 p.His46Arg (c.137A>G) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about BCAT2 p.His46Arg (c.137A>G)?

AlphaMissense predicts likely benign (score 0.0522) — an in-silico prediction, not a clinical call.

BCAT2 p.His46Arg

c.137A>G · rs201148940 · VCV1525411

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0522 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0522	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -2.51	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 0.37	GERP -1.3, phastCons 0.13
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic
Overall
CADD	8.085	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 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.0254% 410/1,613,760 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
South Asian	0.034%	2,938
East Asian	0.0334%	2,991
Admixed American	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0288%	3,471
European (non-Finnish)	0.0261%	3,831
Finnishnot grpmax-eligible	0.00941%	10,626
African / African-American	0.004%	25,020
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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: BCAT2
Protein: p.His46Arg
Coding: c.137A>G
MANE Select: NM_001190
dbSNP: rs201148940
Type: single nucleotide variant
Location: chr19:48806680 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 46: an α-helix

Full BCAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAT2 p.His46_Pro49del Pathogenic same residue
BCAT2 p.Ala188Thr Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg133His Uncertain significance ★★ same type
BCAT2 p.Arg247Trp Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg325Trp Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg333Gly Uncertain significance ★★ ⚠ same type
BCAT2 p.Arg371His Uncertain significance ★★ ⚠ same type
BCAT2 p.Asp112Asn 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/bcat2-p-his46arg (accessed [today's date]).

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