Is BCHE p.Ile34fs (c.100del) pathogenic?

BCHE p.Ile34fs (c.100del) is classified Pathogenic in BCHE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-10). Very rare (popmax 0.00653%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Ile34fs (c.100del)?

BCHE p.Ile34fs (c.100del) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Ile34fs (c.100del) in the general population?

BCHE p.Ile34fs (c.100del) is very rare (popmax 0.00653%, nfe) (gnomAD).

How is Hereditary butyrylcholinesterase deficiency inherited?

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

BCHE p.Ile34fs

c.100del · rs750309713 · VCV594478

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00653%, 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 11	GERP 2.2, phastCons 1
Overall
CADD	20.5	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 0.00653% European (non-Finnish) · 77/1,179,908 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00483% 78/1,613,820 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00653%	15,323
African / African-American	0.00133%	74,920

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.Ile34fs
Coding: c.100del
MANE Select: NM_000055
dbSNP: rs750309713
Type: Deletion
Location: chr3:165830934 (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 34: a β-strand

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.Asn173_Tyr174insTer Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Pro387fs Likely pathogenic ★★ same condition
BCHE p.Arg166fs Likely pathogenic ★ same condition
BCHE p.Tyr265fs Likely pathogenic ★ same condition
BCHE p.Ala230fs Likely pathogenic same condition
BCHE p.Arg414fs Likely pathogenic same condition
BCHE p.Gln204fs Likely pathogenic same condition
BCHE p.Glu165fs 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-ile34fs (accessed [today's date]).

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