Is BCHE p.Arg452Ter (c.1354C>T) pathogenic?

BCHE p.Arg452Ter (c.1354C>T) is classified Pathogenic/Likely pathogenic in BCHE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-01-02). Ultra-rare (popmax 0.0446%, eas); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Arg452Ter (c.1354C>T)?

BCHE p.Arg452Ter (c.1354C>T) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Arg452Ter (c.1354C>T) in the general population?

BCHE p.Arg452Ter (c.1354C>T) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

How is Hereditary butyrylcholinesterase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BCHE p.Arg452Ter

c.1354C>T · rs530517316 · VCV1324370

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.86 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0446% East Asian · 20/44,862 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00254% 41/1,613,760 alleles · ultra-rare exomes 34/1,461,698 · genomes 7/152,062 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,243
Remaining individualsnot grpmax-eligible	0.0112%	8,928
Admixed American	0.00668%	14,980
South Asian	0.0011%	91,068
European (non-Finnish)	0.000763%	131,101

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: BCHE
Protein: p.Arg452Ter
Coding: c.1354C>T
MANE Select: NM_000055
dbSNP: rs530517316
Type: single nucleotide variant
Location: chr3:165829680 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 111 PDB
Residue 452: an α-helix

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

Disease context

butyrylcholinesterase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary butyrylcholinesterase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

BCHE p.Arg414Cys Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Asp98Gly Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Glu377Ter Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Gly143Asp Pathogenic ★★ same condition
BCHE p.Gly393Arg Pathogenic ★★ same condition
BCHE p.Leu358Ile Pathogenic/Likely pathogenic ★★ ⚠ same condition
BCHE p.Tyr528Ter Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Val170Met Likely pathogenic ★★ same condition

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/bche-p-arg452ter (accessed [today's date]).

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