Is BCHE p.Glu525Val (c.1574A>T) pathogenic?

BCHE p.Glu525Val (c.1574A>T) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-18). AlphaMissense: likely benign (0.1852); Very rare (popmax 0.00331%, nfe).

How common is BCHE p.Glu525Val (c.1574A>T) in the general population?

BCHE p.Glu525Val (c.1574A>T) is very rare (popmax 0.00331%, nfe) (gnomAD).

What do computational predictors say about BCHE p.Glu525Val (c.1574A>T)?

AlphaMissense predicts likely benign (score 0.1852) — an in-silico prediction, not a clinical call.

BCHE p.Glu525Val

c.1574A>T · rs121918556 · VCV13221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1852	likely benign
REVEL	0.598	indeterminate
SaProt	LLR -11.06	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 6.1	GERP 0.4, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	22.0	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 0.00331% European (non-Finnish) · 39/1,178,750 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00248% 40/1,612,136 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,224
Remaining individualsnot grpmax-eligible	0.0016%	62,382

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.Glu525Val
Coding: c.1574A>T
MANE Select: NM_000055
dbSNP: rs121918556
Type: single nucleotide variant
Location: chr3:165786255 (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 525: a turn; a disulfide bond; a UniProt-annotated variant site (in bched; allele j variant)

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

Similar variants

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BCHE p.Arg452Ter Pathogenic/Likely pathogenic ★★ same type
BCHE p.Asp98Gly Pathogenic/Likely pathogenic ★★ ⚠ same type
BCHE p.Glu377Ter Pathogenic/Likely pathogenic ★★ same type
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-glu525val (accessed [today's date]).

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