Is BCHE p.Asp368Val (c.1103A>T) pathogenic?

BCHE p.Asp368Val (c.1103A>T) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.2471); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with BCHE p.Asp368Val (c.1103A>T)?

BCHE p.Asp368Val (c.1103A>T) is associated with Inborn genetic diseases (ClinVar).

How common is BCHE p.Asp368Val (c.1103A>T) in the general population?

BCHE p.Asp368Val (c.1103A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BCHE p.Asp368Val (c.1103A>T)?

AlphaMissense predicts likely benign (score 0.2471) — an in-silico prediction, not a clinical call.

BCHE p.Asp368Val

c.1103A>T · VCV3823352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2471 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2471	likely benign
REVEL	0.803	moderately pathogenic-leaning
SaProt	LLR -7.65	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	25.3	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 0.00167% Admixed American · 1/59,820 alleles

Overall 6.2e-05% 1/1,613,578 alleles · very rare exomes 1/1,461,312 · genomes 0/152,266 · joint denominator

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.Asp368Val
Coding: c.1103A>T
MANE Select: NM_000055
Type: single nucleotide variant
Location: chr3:165829931 (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 368: a β-strand

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.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
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-asp368val (accessed [today's date]).

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