Is BCHE p.Thr52Met (c.155C>T) pathogenic?

BCHE p.Thr52Met (c.155C>T) is classified Uncertain significance in BCHE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-05-05). AlphaMissense: likely benign (0.0833); Ultra-rare (popmax 0.0453%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Thr52Met (c.155C>T)?

BCHE p.Thr52Met (c.155C>T) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Thr52Met (c.155C>T) in the general population?

BCHE p.Thr52Met (c.155C>T) is ultra-rare (popmax 0.0453%, 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.Thr52Met (c.155C>T)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

BCHE p.Thr52Met

c.155C>T · rs56309853 · VCV550834

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.615	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP 1.6, phastCons 0.93
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	16.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0453% European (non-Finnish) · 535/1,179,900 alleles

Filtering AF 0.0421% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0409%

Overall 0.0351% 566/1,613,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0453%	2,205
East Asian	0.0178%	5,608
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Finnishnot grpmax-eligible	0.00937%	10,668
African / African-American	0.00667%	15,003
South Asian	0.0011%	91,082

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.Thr52Met
Coding: c.155C>T
MANE Select: NM_000055
dbSNP: rs56309853
Type: single nucleotide variant
Location: chr3:165830879 (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 52: a UniProt-annotated variant site (in bched); 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.Thr52= Likely benign ★★ same residue
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

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-thr52met (accessed [today's date]).

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