Is BCHE p.Val170Met (c.508G>A) pathogenic?

BCHE p.Val170Met (c.508G>A) is classified Likely pathogenic in BCHE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-19). AlphaMissense: ambiguous (0.4657); Very rare (popmax 0.00432%, nfe); Associated with butyrylcholinesterase deficiency.

What condition is associated with BCHE p.Val170Met (c.508G>A)?

BCHE p.Val170Met (c.508G>A) is associated with butyrylcholinesterase deficiency (ClinVar).

How common is BCHE p.Val170Met (c.508G>A) in the general population?

BCHE p.Val170Met (c.508G>A) is very rare (popmax 0.00432%, 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.Val170Met (c.508G>A)?

AlphaMissense predicts ambiguous (score 0.4657) — an in-silico prediction, not a clinical call.

BCHE p.Val170Met

c.508G>A · rs527843566 · VCV13217

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

butyrylcholinesterase deficiency

Computational evidence

Protein change
AlphaMissense	0.4657	ambiguous
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -14.11	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 2.4, phastCons 0.99
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	24.7	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 0.00432% European (non-Finnish) · 51/1,179,950 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00316% 51/1,613,846 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.Val170Met
Coding: c.508G>A
MANE Select: NM_000055
dbSNP: rs527843566
Type: single nucleotide variant
Location: chr3:165830526 (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 170: a UniProt-annotated variant site (in bched; allele h variant); 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.Val170Ala 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-val170met (accessed [today's date]).

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