Is CPE p.Asp251= (c.753C>T) pathogenic?

CPE p.Asp251= (c.753C>T) is classified Likely benign in CPE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-21). Ultra-rare (popmax 0.0187%, afr); Associated with CPE-related disorder.

What condition is associated with CPE p.Asp251= (c.753C>T)?

CPE p.Asp251= (c.753C>T) is associated with CPE-related disorder (ClinVar).

How common is CPE p.Asp251= (c.753C>T) in the general population?

CPE p.Asp251= (c.753C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

CPE p.Asp251=

c.753C>T · VCV3352972

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

CPE-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.7, phastCons 1
Overall
CADD	7.469	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,902 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.000992% 16/1,613,706 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,350
Remaining individualsnot grpmax-eligible	0.0016%	62,480
South Asian	0.0011%	91,070

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.Asp251=
Coding: c.753C>T
MANE Select: NM_001873
Type: single nucleotide variant
Location: chr4:165482322 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83
Residue 251: 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

CPE-related disorder

Similar variants

CPE p.Asp251Gly Uncertain significance ★★ ⚠ same residue
CPE p.Arg121Ter Pathogenic ★★ same condition
CPE c.974-3C>T Uncertain significance ★ same condition
CPE p.Ile415Met Uncertain significance ★ ⚠ same condition
CPE p.Pro30Ala Uncertain significance ★ ⚠ same condition
CPE c.673-2A>G Uncertain significance same condition
CPE p.Ala231Gly Uncertain significance ⚠ same condition
CPE p.Ala266Ser 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/cpe-p-asp251 (accessed [today's date]).

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