Is BCHE p.Phe392Ter (c.1171_1174dup) pathogenic?

BCHE p.Phe392Ter (c.11711174dup) is classified Likely pathogenic in BCHE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). Ultra-rare (gnomAD MAF 3.365e-06); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Phe392Ter (c.1171_1174dup)?

BCHE p.Phe392Ter (c.1171_1174dup) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Phe392Ter (c.1171_1174dup) in the general population?

BCHE p.Phe392Ter (c.1171_1174dup) is ultra-rare (gnomAD MAF 3.365e-06) (gnomAD).

How is Hereditary butyrylcholinesterase deficiency inherited?

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

BCHE p.Phe392Ter

c.1171_1174dup · rs759679732 · VCV2501206

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 3.365e-06)

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	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000336% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: BCHE
Protein: p.Phe392Ter
Coding: c.1171_1174dup
MANE Select: NM_000055
dbSNP: rs759679732
Type: Microsatellite
Location: chr3:165829859 (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 392: 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.Phe392Leu Uncertain significance ★ ⚠ same residue
BCHE p.Phe223fs Likely pathogenic same condition
BCHE p.Val421del Uncertain significance same condition
BCHE p.Arg414Cys Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Arg452Ter Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Asn173_Tyr174insTer Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Asp98Gly Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Glu377Ter 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-phe392ter (accessed [today's date]).

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