Is BCHE p.Pro363Thr (c.1087C>A) pathogenic?

BCHE p.Pro363Thr (c.1087C>A) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.1218); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BCHE p.Pro363Thr (c.1087C>A)?

BCHE p.Pro363Thr (c.1087C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BCHE p.Pro363Thr (c.1087C>A) in the general population?

BCHE p.Pro363Thr (c.1087C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCHE p.Pro363Thr (c.1087C>A)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

BCHE p.Pro363Thr

c.1087C>A · rs757948667 · VCV3133356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -9.30	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 10	GERP 1.8, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCHE
Protein: p.Pro363Thr
Coding: c.1087C>A
MANE Select: NM_000055
dbSNP: rs757948667
Type: single nucleotide variant
Location: chr3:165829947 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 111 PDB

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

BCHE p.Pro363Ser Uncertain significance ★ ⚠ same residue
BCHE p.Ile538Thr Uncertain significance ★★ ⚠ same condition
BCHE p.Met109Ile Uncertain significance ★★ ⚠ same condition
BCHE p.Ser515Thr Uncertain significance ★★ ⚠ same condition
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

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-pro363thr (accessed [today's date]).

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