PDE2A p.Ala518=
c.1554C>G · rs116776002 · VCV1671231
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.69%, 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 -2.9 | GERP -3.2 |
| Overall | ||
| CADD | 3.045 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.69%
African / African-American · 1,268/74,954 alleles
Filtering AF
1.61%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.58%
Overall
0.0881%
1,420/1,610,946 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.69% | 59 |
| Remaining individualsnot grpmax-eligible | 0.119% | 843 |
| Admixed American | 0.075% | 1,334 |
| Middle Eastern | 0.033% | 3,027 |
| European (non-Finnish) | 0.00246% | 40,593 |
| East Asian | 0.00223% | 44,856 |
| South Asian | 0.0011% | 90,986 |
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.Ala518=
- Coding
- c.1554C>G
- MANE Select
- NM_002599
- dbSNP
- rs116776002
- Type
- single nucleotide variant
- Location
- chr11:72584297 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.17 · 44 PDB
- Residue 518
- a UniProt-annotated variant site (in iddpads); the gaf 3 domain; a β-strand
Similar variants
- 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
- PDE2A p.Asp59Asn 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-ala518 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown