Is BCHE p.Tyr61Cys (c.182A>G) pathogenic?

BCHE p.Tyr61Cys (c.182A>G) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 2 submitters; last evaluated 2022-05-10). AlphaMissense: ambiguous (0.4938); Very rare (popmax 0.00769%, sas); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Tyr61Cys (c.182A>G)?

BCHE p.Tyr61Cys (c.182A>G) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Tyr61Cys (c.182A>G) in the general population?

BCHE p.Tyr61Cys (c.182A>G) is very rare (popmax 0.00769%, sas) (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.Tyr61Cys (c.182A>G)?

AlphaMissense predicts ambiguous (score 0.4938) — an in-silico prediction, not a clinical call.

BCHE p.Tyr61Cys

c.182A>G · rs116097205 · VCV555005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.4938	ambiguous
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -13.28	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	27.7	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 0.00769% South Asian · 7/91,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000744% 12/1,613,840 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
East Asian	0.00223%	44,878
European (non-Finnish)	0.000339%	294,985

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.Tyr61Cys
Coding: c.182A>G
MANE Select: NM_000055
dbSNP: rs116097205
Type: single nucleotide variant
Location: chr3:165830852 (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 61: a UniProt-annotated variant site (in bched; enzymatically inactive in the plasma)

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.Arg414Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
BCHE p.Arg452Ter Pathogenic/Likely pathogenic ★★ same condition
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-tyr61cys (accessed [today's date]).

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