PDE2A p.Pro149=
c.447G>A · rs956348156 · VCV1653974
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.41 | GERP -3.5, phastCons 0.057 |
| Overall | ||
| CADD | 7.357 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
African / African-American · 11/71,460 alleles
Filtering AF
0.00853%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.00132%
20/1,512,384 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0154% | 6,496 |
| South Asian | 0.00263% | 38,074 |
| European (non-Finnish) | 0.000624% | 160,365 |
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.Pro149=
- Coding
- c.447G>A
- MANE Select
- NM_002599
- dbSNP
- rs956348156
- Type
- single nucleotide variant
- Location
- chr11:72596635 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.17 · 44 PDB
- Residue 149
- the gaf 1 domain; a UniProt-annotated variant site (in iddpads; uncertain significance)
Similar variants
- PDE2A p.Pro149Leu Pathogenic same residue
- PDE2A c.1922+4C>T Uncertain significance ★★ same type
- PDE2A p.Ala157Val Uncertain significance ★★ ⚠ same type
- PDE2A p.Ala205Val Uncertain significance ★★ ⚠ same type
- PDE2A p.Ala349Thr Uncertain significance ★★ ⚠ same type
- PDE2A p.Arg226Cys Uncertain significance ★★ ⚠ same type
- PDE2A p.Arg790Gln Uncertain significance ★★ ⚠ same type
- PDE2A p.Asp34Glu Uncertain significance ★★ ⚠ 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-pro149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown