Is BCHE p.Glu283Asp (c.849G>C) pathogenic?

BCHE p.Glu283Asp (c.849G>C) is classified Conflicting classifications of pathogenicity in BCHE (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0736); Common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Glu283Asp (c.849G>C)?

BCHE p.Glu283Asp (c.849G>C) is associated with butyrylcholinesterase deficiency (ClinVar).

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.Glu283Asp (c.849G>C)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

BCHE p.Glu283Asp

Q: How common is BCHE p.Glu283Asp (c.849G>C) in the general population?

BCHE p.Glu283Asp (c.849G>C) is common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.849G>C · rs16849700 · VCV254777

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.068	GERP -3.3, phastCons 0.73
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	1.228	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 5.9% African / African-American · 4,425/75,000 alleles

Filtering AF 5.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.7%

Overall 1.53% 24,760/1,613,926 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.9%	17
Middle Eastern	4.22%	24
South Asian	2.64%	38
Remaining individualsnot grpmax-eligible	1.75%	57
European (non-Finnish)	1.32%	76
Ashkenazi Jewishnot grpmax-eligible	1.13%	88
Admixed American	0.886%	113
Finnishnot grpmax-eligible	0.233%	430
East Asian	0.00891%	11,218

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.Glu283Asp
Coding: c.849G>C
MANE Select: NM_000055
dbSNP: rs16849700
Type: single nucleotide variant
Location: chr3:165830185 (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 283: a disulfide bond; a UniProt-annotated variant site (in)

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-glu283asp (accessed [today's date]).

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