Is BCHE p.Tyr156Cys (c.467A>G) pathogenic?

BCHE p.Tyr156Cys (c.467A>G) is classified Pathogenic in BCHE (ClinVar, No assertion criteria, 1 submitter; last evaluated 1997-11-01). AlphaMissense: ambiguous (0.3727); Very rare (popmax 0.000169%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Tyr156Cys (c.467A>G)?

BCHE p.Tyr156Cys (c.467A>G) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Tyr156Cys (c.467A>G) in the general population?

BCHE p.Tyr156Cys (c.467A>G) is very rare (popmax 0.000169%, nfe) (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.Tyr156Cys (c.467A>G)?

AlphaMissense predicts ambiguous (score 0.3727) — an in-silico prediction, not a clinical call.

BCHE p.Tyr156Cys

c.467A>G · rs121918558 · VCV13227

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.3727	ambiguous
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -13.61	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	26.8	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 0.000169% European (non-Finnish) · 2/1,179,952 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,714 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)grpmax	0.000169%	589,977

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr156Cys
Coding: c.467A>G
MANE Select: NM_000055
dbSNP: rs121918558
Type: single nucleotide variant
Location: chr3:165830567 (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 156: a UniProt-annotated variant site (in bched); 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

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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
BCHE p.Tyr528Ter 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-tyr156cys (accessed [today's date]).

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