Is BCHE p.Asp482Glu (c.1446T>A) pathogenic?

BCHE p.Asp482Glu (c.1446T>A) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely benign (0.0862); Very rare (popmax 0.00501%, amr); Associated with Inborn genetic diseases.

What condition is associated with BCHE p.Asp482Glu (c.1446T>A)?

BCHE p.Asp482Glu (c.1446T>A) is associated with Inborn genetic diseases (ClinVar).

How common is BCHE p.Asp482Glu (c.1446T>A) in the general population?

BCHE p.Asp482Glu (c.1446T>A) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about BCHE p.Asp482Glu (c.1446T>A)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

BCHE p.Asp482Glu

c.1446T>A · VCV3823363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -5.70	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 0.2	GERP -3.6
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	8.726	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 0.00501% Admixed American · 3/59,940 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000274% 4/1,461,600 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,980
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Asp482Glu
Coding: c.1446T>A
MANE Select: NM_000055
Type: single nucleotide variant
Location: chr3:165829588 (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 482: an α-helix; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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BCHE p.Ala430Asp Uncertain significance ★ ⚠ same condition
BCHE p.Ala444Thr Uncertain significance ★ ⚠ same condition
BCHE p.Ala544Pro Uncertain significance ★ ⚠ same condition
BCHE p.Ala544Val Uncertain significance ★ ⚠ same condition
BCHE p.Ala567Val Uncertain significance ★ ⚠ 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-asp482glu (accessed [today's date]).

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