Is PDE2A p.Pro38_Pro40del (c.107CGC[2]) pathogenic?

PDE2A p.Pro38Pro40del (c.107CGC[2]) is classified Uncertain significance in PDE2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). Ultra-rare (popmax 0.0682%, mid).

How common is PDE2A p.Pro38_Pro40del (c.107CGC[2]) in the general population?

PDE2A p.Pro38_Pro40del (c.107CGC[2]) is ultra-rare (popmax 0.0682%, mid) (gnomAD).

PDE2A p.Pro38_Pro40del

c.107CGC[2] · rs761717652 · VCV1501449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0682%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.74, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(GGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0682% Middle Eastern · 4/5,862 alleles

Filtering AF 0.0233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.00616% 94/1,525,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0682%	1,465
South Asian	0.0327%	3,059
Ashkenazi Jewishnot grpmax-eligible	0.0295%	3,385
Remaining individualsnot grpmax-eligible	0.0119%	8,417
Admixed American	0.00842%	11,872
European (non-Finnish)	0.0036%	27,790
Finnishnot grpmax-eligible	0.00343%	29,133
East Asian	0.00264%	37,808
African / African-American	0.00143%	69,926

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: PDE2A
Protein: p.Pro38_Pro40del
Coding: c.107CGC[2]
MANE Select: NM_002599
dbSNP: rs761717652
Type: Microsatellite
Location: chr11:72642277 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 44 PDB
Residue 38: the 'disordered' region

Full PDE2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE2A p.Pro38Gln Uncertain significance ★ ⚠ same residue
PDE2A p.Pro38Ser Uncertain significance ★ ⚠ same residue
PDE2A c.1728+15_1728+16del 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/pde2a-p-pro38-pro40del (accessed [today's date]).

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