Is BCHE p.Trp499Ter (c.1497G>A) pathogenic?

BCHE p.Trp499Ter (c.1497G>A) is classified Likely pathogenic in BCHE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-11-16). Absent from gnomAD v4.1; Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Trp499Ter (c.1497G>A)?

BCHE p.Trp499Ter (c.1497G>A) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Trp499Ter (c.1497G>A) in the general population?

BCHE p.Trp499Ter (c.1497G>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary butyrylcholinesterase deficiency inherited?

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

BCHE p.Trp499Ter

c.1497G>A · rs1553778017 · VCV555018

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Pangolin	Δ0.41	gain · loss 0.32 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCHE
Protein: p.Trp499Ter
Coding: c.1497G>A
MANE Select: NM_000055
dbSNP: rs1553778017
Type: single nucleotide variant
Location: chr3:165829537 (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 499: an α-helix; a disulfide bond; a UniProt-annotated variant site (in bched; seems to cause reduced expression of the protein)

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.Trp499Arg Likely pathogenic ★ same residue
BCHE p.Arg414Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
BCHE p.Arg452Ter 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

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-trp499ter (accessed [today's date]).

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