Is BCAT2 p.Pro208= (c.624G>A) pathogenic?

BCAT2 p.Pro208= (c.624G>A) is classified Benign in BCAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). Ultra-rare (popmax 0.0463%, amr).

How common is BCAT2 p.Pro208= (c.624G>A) in the general population?

BCAT2 p.Pro208= (c.624G>A) is ultra-rare (popmax 0.0463%, amr) (gnomAD).

BCAT2 p.Pro208=

c.624G>A · rs369994559 · VCV2055200

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0463%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.3	GERP -4
Overall
CADD	0.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0463% Admixed American · 25/53,970 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0275%

Overall 0.0302% 479/1,585,092 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.05%	96
Remaining individualsnot grpmax-eligible	0.0927%	1,079
Admixed Americangrpmax	0.0463%	2,159
Middle Eastern	0.0166%	6,014
European (non-Finnish)	0.00789%	12,680
Finnishnot grpmax-eligible	0.00162%	61,816
African / African-American	0.00134%	74,784

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.Pro208=
Coding: c.624G>A
MANE Select: NM_001190
dbSNP: rs369994559
Type: single nucleotide variant
Location: chr19:48799746 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.47 · 30 PDB
Residue 208: 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.Pro208Ser Uncertain significance ★★ ⚠ 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-pro208 (accessed [today's date]).

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