Is BCHE p.Lys40Arg (c.119A>G) pathogenic?

BCHE p.Lys40Arg (c.119A>G) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0625); Rare (popmax 0.625%, afr).

How common is BCHE p.Lys40Arg (c.119A>G) in the general population?

BCHE p.Lys40Arg (c.119A>G) is rare (popmax 0.625%, afr) (gnomAD).

What do computational predictors say about BCHE p.Lys40Arg (c.119A>G)?

AlphaMissense predicts likely benign (score 0.0625) — an in-silico prediction, not a clinical call.

BCHE p.Lys40Arg

c.119A>G · rs116047990 · VCV3063838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0625 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.625%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0625	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.78	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 1.8	GERP -0.86, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	11.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.625% African / African-American · 469/75,034 alleles

Filtering AF 0.578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.56%

Overall 0.0336% 543/1,613,930 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.625%	160
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Admixed American	0.0467%	2,141
Middle Eastern	0.033%	3,030
South Asian	0.0011%	91,084
European (non-Finnish)	8.48e-05%	1,179,903

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.Lys40Arg
Coding: c.119A>G
MANE Select: NM_000055
dbSNP: rs116047990
Type: single nucleotide variant
Location: chr3:165830915 (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 40: a UniProt-annotated variant site (does not affect enzymatic activity); a β-strand

Full BCHE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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-lys40arg (accessed [today's date]).

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