Is BCAT2 p.Pro215Arg (c.644C>G) pathogenic?

BCAT2 p.Pro215Arg (c.644C>G) is classified Conflicting classifications of pathogenicity in BCAT2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-03). AlphaMissense: ambiguous (0.3512); Ultra-rare (popmax 0.0393%, amr).

How common is BCAT2 p.Pro215Arg (c.644C>G) in the general population?

BCAT2 p.Pro215Arg (c.644C>G) is ultra-rare (popmax 0.0393%, amr) (gnomAD).

What do computational predictors say about BCAT2 p.Pro215Arg (c.644C>G)?

AlphaMissense predicts ambiguous (score 0.3512) — an in-silico prediction, not a clinical call.

BCAT2 p.Pro215Arg

c.644C>G · rs150646107 · VCV732830

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3512 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0393%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3512	ambiguous
REVEL	0.26	benign-leaning
SaProt	LLR -13.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.055 · regional, not allelic
Overall
CADD	27.8	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 0.0393% Admixed American · 22/55,940 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.0226% 361/1,595,364 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.252%	397
Admixed Americangrpmax	0.0393%	2,543
Remaining individualsnot grpmax-eligible	0.034%	2,943
European (non-Finnish)	0.0206%	4,845
African / African-American	0.00401%	24,928

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro215Arg
Coding: c.644C>G
MANE Select: NM_001190
dbSNP: rs150646107
Type: single nucleotide variant
Location: chr19:48799726 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 215: a UniProt-annotated variant site (in hvli)

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

Similar variants

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
BCAT2 p.Asp259Asn 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-pro215arg (accessed [today's date]).

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