Is CPE p.Ala15= (c.45A>G) pathogenic?

CPE p.Ala15= (c.45A>G) is classified Likely benign in CPE (ClinVar, Single submitter, 2 submitters; last evaluated 2020-02-07). Ultra-rare (popmax 0.0103%, afr).

How common is CPE p.Ala15= (c.45A>G) in the general population?

CPE p.Ala15= (c.45A>G) is ultra-rare (popmax 0.0103%, afr) (gnomAD).

CPE p.Ala15=

c.45A>G · VCV3350553

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, afr)

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 -2.2	GERP -4.8
Overall
CADD	5.366	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% African / African-American · 7/67,976 alleles

Filtering AF 0.00477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00334%

Overall 0.000689% 10/1,450,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0103%	9,711
East Asian	0.00513%	19,492
South Asian	0.00142%	70,182

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.Ala15=
Coding: c.45A>G
MANE Select: NM_001873
Type: single nucleotide variant
Location: chr4:165379266 (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

Similar variants

CPE p.Ala15Thr Uncertain significance ★ ⚠ same residue
CPE p.Arg121Ter Pathogenic ★★ same type
CPE p.Arg262Trp Uncertain significance ★★ ⚠ same type
CPE p.Arg297Trp Uncertain significance ★★ ⚠ same type
CPE p.Asp251Gly Uncertain significance ★★ ⚠ same type
CPE p.Asp304Ala Uncertain significance ★★ ⚠ same type
CPE p.Trp21Cys Uncertain significance ★★ ⚠ same type
CPE c.307+13C>T 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-ala15 (accessed [today's date]).

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