Is CPE p.Glu26fs (c.76_98del) pathogenic?

CPE p.Glu26fs (c.7698del) is classified Pathogenic in CPE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-11-01). Very rare (popmax 0.00248%, eas); Associated with BDV syndrome.

What condition is associated with CPE p.Glu26fs (c.76_98del)?

CPE p.Glu26fs (c.76_98del) is associated with BDV syndrome (ClinVar).

How common is CPE p.Glu26fs (c.76_98del) in the general population?

CPE p.Glu26fs (c.76_98del) is very rare (popmax 0.00248%, eas) (gnomAD).

CPE p.Glu26fs

c.76_98del · rs768504422 · VCV689401

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00248%, eas)

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 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 1.6, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00248% East Asian · 1/40,366 alleles

Filtering AF 0.000257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000165%

Overall 0.00074% 10/1,352,120 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00248%	40,366
Remaining individualsnot grpmax-eligible	0.00172%	58,044
South Asian	0.00125%	79,990
European (non-Finnish)	0.000617%	162,118

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: CPE
Protein: p.Glu26fs
Coding: c.76_98del
MANE Select: NM_001873
dbSNP: rs768504422
Type: Deletion
Location: chr4:165379290 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83

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.Ser333fs Pathogenic ★ same condition
CPE p.Glu26Ala Uncertain significance ★ ⚠ same residue
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-glu26fs (accessed [today's date]).

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