Is BCHE p.Thr246Pro (c.736A>C) pathogenic?

BCHE p.Thr246Pro (c.736A>C) is classified Uncertain significance in BCHE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.1582); Absent from gnomAD v4.1; Associated with BCHE-related disorder.

What condition is associated with BCHE p.Thr246Pro (c.736A>C)?

BCHE p.Thr246Pro (c.736A>C) is associated with BCHE-related disorder (ClinVar).

How common is BCHE p.Thr246Pro (c.736A>C) in the general population?

BCHE p.Thr246Pro (c.736A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCHE p.Thr246Pro (c.736A>C)?

AlphaMissense predicts likely benign (score 0.1582) — an in-silico prediction, not a clinical call.

BCHE p.Thr246Pro

c.736A>C · rs1714913880 · VCV3029270

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1582 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BCHE-related disorder

Computational evidence

Protein change
AlphaMissense	0.1582	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -3.5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	23.1	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

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.Thr246Pro
Coding: c.736A>C
MANE Select: NM_000055
dbSNP: rs1714913880
Type: single nucleotide variant
Location: chr3:165830298 (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 246: a β-strand

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

Disease context

BCHE-related disorder

Similar variants

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BCHE p.Phe146fs Pathogenic ★★ same condition
BCHE p.Leu121fs Likely pathogenic ★ same condition
BCHE p.Arg414Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
BCHE p.Arg452Ter Pathogenic/Likely pathogenic ★★ same type
BCHE p.Glu377Ter Pathogenic/Likely pathogenic ★★ same type

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-thr246pro (accessed [today's date]).

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