Is BCHE p.Ala212Val (c.635C>T) pathogenic?

BCHE p.Ala212Val (c.635C>T) is classified Conflicting classifications of pathogenicity in BCHE (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-03-03). AlphaMissense: likely benign (0.0825); Rare (popmax 0.478%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Ala212Val (c.635C>T)?

BCHE p.Ala212Val (c.635C>T) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Ala212Val (c.635C>T) in the general population?

BCHE p.Ala212Val (c.635C>T) is rare (popmax 0.478%, 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.Ala212Val (c.635C>T)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

BCHE p.Ala212Val

c.635C>T · rs114706984 · VCV370854

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.478%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
REVEL	0.365	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 0.99
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	18.21	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 0.478% European (non-Finnish) · 5,641/1,179,918 alleles

Filtering AF 0.468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.463%

Overall 0.377% 6,090/1,613,890 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.478%	209
Ashkenazi Jewishnot grpmax-eligible	0.324%	308
Remaining individualsnot grpmax-eligible	0.275%	363
Admixed American	0.117%	857
African / African-American	0.0893%	1,119
Finnishnot grpmax-eligible	0.0281%	3,556
South Asian	0.0275%	3,643
Middle Eastern	0.0165%	6,060

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.Ala212Val
Coding: c.635C>T
MANE Select: NM_000055
dbSNP: rs114706984
Type: single nucleotide variant
Location: chr3:165830399 (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 212: 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.Glu377Ter Pathogenic/Likely pathogenic ★★ same condition
BCHE p.Gly143Asp Pathogenic ★★ same condition
BCHE p.Gly393Arg Pathogenic ★★ same condition
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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-ala212val (accessed [today's date]).

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