Is CPE p.Ser333fs (c.994del) pathogenic?

CPE p.Ser333fs (c.994del) is classified Pathogenic in CPE (ClinVar, Single submitter, 2 submitters; last evaluated 2018-10-20). Absent from gnomAD; Associated with BDV syndrome.

What condition is associated with CPE p.Ser333fs (c.994del)?

CPE p.Ser333fs (c.994del) is associated with BDV syndrome (ClinVar).

How common is CPE p.Ser333fs (c.994del) in the general population?

CPE p.Ser333fs (c.994del) is absent from gnomAD (gnomAD).

CPE p.Ser333fs

c.994del · rs1579283609 · VCV649127

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

BDV syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CPE
Protein: p.Ser333fs
Coding: c.994del
MANE Select: NM_001873
dbSNP: rs1579283609
Type: Deletion
Location: chr4:165487457 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83
Residue 333: a UniProt-annotated variant site (in bdvs); the peptidase m14 domain

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

Disease context

BDV syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CPE-related Prader-Willi-like syndrome (Orphanet):

Onset: Childhood, Infancy

Similar variants

CPE p.Ser333Gly Uncertain significance ★ ⚠ same residue
CPE p.Glu26fs Pathogenic same condition
CPE p.Arg121Ter Pathogenic ★★ same condition
CPE c.505-3dup Benign/Likely benign ★★ same condition
CPE p.Leu474= Benign/Likely benign ★★ same condition
CPE p.Ser404fs Likely pathogenic ★ same condition
CPE p.Tyr135Ter Pathogenic same condition
CPE c.505-3del Likely benign ★ 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/cpe-p-ser333fs (accessed [today's date]).

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