Is BCHE p.Ala62Val (c.185C>T) pathogenic?

BCHE p.Ala62Val (c.185C>T) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-30). AlphaMissense: likely pathogenic (0.7006); Very rare (popmax 8.48e-05%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Ala62Val (c.185C>T)?

BCHE p.Ala62Val (c.185C>T) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Ala62Val (c.185C>T) in the general population?

BCHE p.Ala62Val (c.185C>T) is very rare (popmax 8.48e-05%, 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.Ala62Val (c.185C>T)?

AlphaMissense predicts likely pathogenic (score 0.7006) — an in-silico prediction, not a clinical call.

BCHE p.Ala62Val

c.185C>T · rs1553778274 · VCV550396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.7006	likely pathogenic
REVEL	0.942	strongly pathogenic-leaning
SaProt	LLR -11.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2.4, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,916 alleles

Overall 6.84e-05% 1/1,461,696 alleles · very rare

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.Ala62Val
Coding: c.185C>T
MANE Select: NM_000055
dbSNP: rs1553778274
Type: single nucleotide variant
Location: chr3:165830849 (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 62: a UniProt-annotated variant site (in bched; reduced enzyme activity with butyrylthiocholine as substrate; inactive with butyrylthiocholine as substrate in the presence of g-98; 2-fold lower affinity for butyrylthiocholine; 10-fold lower affinity for butyrylthiocholine in the presence of g-98)

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.Ala62= Uncertain significance ★ 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-ala62val (accessed [today's date]).

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