Is BCHE p.Ile384Val (c.1150A>G) pathogenic?

BCHE p.Ile384Val (c.1150A>G) is classified Conflicting classifications of pathogenicity in BCHE (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.0707); Rare (popmax 0.155%, amr); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Ile384Val (c.1150A>G)?

BCHE p.Ile384Val (c.1150A>G) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Ile384Val (c.1150A>G) in the general population?

BCHE p.Ile384Val (c.1150A>G) is rare (popmax 0.155%, amr) (gnomAD).

How is Hereditary butyrylcholinesterase deficiency inherited?

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

What do computational predictors say about BCHE p.Ile384Val (c.1150A>G)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

BCHE p.Ile384Val

c.1150A>G · rs146936556 · VCV900999

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.155%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.79	GERP -3.6
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	6.148	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.155% Admixed American · 92/59,352 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.0529% 852/1,611,358 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.155%	645
European (non-Finnish)	0.0611%	1,636
Remaining individualsnot grpmax-eligible	0.045%	2,225
Middle Eastern	0.0165%	6,050
African / African-American	0.0067%	14,923
South Asian	0.00552%	18,126

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.Ile384Val
Coding: c.1150A>G
MANE Select: NM_000055
dbSNP: rs146936556
Type: single nucleotide variant
Location: chr3:165829884 (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 384: 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)

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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-ile384val (accessed [today's date]).

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