Is BCHE p.Leu358fs (c.1073dup) pathogenic?

BCHE p.Leu358fs (c.1073dup) is classified Likely pathogenic in BCHE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-02-02). Very rare (popmax 8.48e-05%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Leu358fs (c.1073dup)?

BCHE p.Leu358fs (c.1073dup) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Leu358fs (c.1073dup) in the general population?

BCHE p.Leu358fs (c.1073dup) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Hereditary butyrylcholinesterase deficiency inherited?

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

BCHE p.Leu358fs

c.1073dup · rs1057516450 · VCV370388

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.056	GERP -3.3, phastCons 0.95

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,884 alleles

Overall 6.84e-05% 1/1,461,532 alleles · very rare

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.Leu358fs
Coding: c.1073dup
MANE Select: NM_000055
dbSNP: rs1057516450
Type: Duplication
Location: chr3:165829960 (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 358: an α-helix; a UniProt-annotated variant site (in bched; bche variant form; fluoride-resistant)

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.Leu358Ile Pathogenic/Likely pathogenic ★★ ⚠ same residue
BCHE p.Thr343fs Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Lys276delinsAsnTer Likely pathogenic ★ same condition
BCHE p.Pro313fs Likely pathogenic ★ same condition
BCHE c.1160_1161ins[N[342];1146_1160] Pathogenic same condition
BCHE p.Trp458fs Likely pathogenic same condition
BCHE p.Glu568_Ala573dup Uncertain significance same condition
BCHE p.Met539fs Uncertain significance 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-leu358fs (accessed [today's date]).

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