Is BCHE p.Asp198Glu (c.594T>G) pathogenic?

BCHE p.Asp198Glu (c.594T>G) is classified Likely pathogenic in BCHE (ClinVar, Single submitter, 2 submitters; last evaluated 2022-03-28). AlphaMissense: likely pathogenic (0.9311); Very rare (popmax 0.00703%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Asp198Glu (c.594T>G)?

BCHE p.Asp198Glu (c.594T>G) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Asp198Glu (c.594T>G) in the general population?

BCHE p.Asp198Glu (c.594T>G) is very rare (popmax 0.00703%, 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.Asp198Glu (c.594T>G)?

AlphaMissense predicts likely pathogenic (score 0.9311) — an in-silico prediction, not a clinical call.

BCHE p.Asp198Glu

c.594T>G · rs781368801 · VCV1677196

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9311 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.9311	likely pathogenic ✓ concordant with ClinVar · top 3% in BCHE
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -13.21	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 1.1	GERP -5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	20.7	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 0.00703% European (non-Finnish) · 83/1,179,886 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.00552% 89/1,613,642 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00703%	14,215
Remaining individualsnot grpmax-eligible	0.0064%	15,616
Admixed American	0.00167%	59,906
African / African-American	0.00134%	74,874

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.Asp198Glu
Coding: c.594T>G
MANE Select: NM_000055
dbSNP: rs781368801
Type: single nucleotide variant
Location: chr3:165830440 (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 198: a UniProt-annotated variant site (in bched; seems to cause reduced expression of the protein); 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-asp198glu (accessed [today's date]).

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