Is BCHE p.Val232Asp (c.695T>A) pathogenic?

BCHE p.Val232Asp (c.695T>A) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-06). AlphaMissense: likely pathogenic (0.8974); Very rare (popmax 0.000169%, nfe).

How common is BCHE p.Val232Asp (c.695T>A) in the general population?

BCHE p.Val232Asp (c.695T>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about BCHE p.Val232Asp (c.695T>A)?

AlphaMissense predicts likely pathogenic (score 0.8974) — an in-silico prediction, not a clinical call.

BCHE p.Val232Asp

c.695T>A · VCV3629791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8974	likely pathogenic · top 4% in BCHE
REVEL	0.997	strongly pathogenic-leaning
SaProt	LLR -16.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000169% European (non-Finnish) · 2/1,179,946 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,698 alleles · very rare

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.Val232Asp
Coding: c.695T>A
MANE Select: NM_000055
Type: single nucleotide variant
Location: chr3:165830339 (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 232: a UniProt-annotated variant site (in bched); an α-helix

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

Similar variants

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BCHE p.Gly143Asp Pathogenic ★★ same type
BCHE p.Gly393Arg Pathogenic ★★ same type
BCHE p.Leu358Ile Pathogenic/Likely pathogenic ★★ ⚠ same type
BCHE p.Tyr528Ter 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-val232asp (accessed [today's date]).

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