PDE2A p.Leu389=
c.1167C>T · rs149180422 · VCV1555741
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0185%, amr)
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 5.7 | GERP 0.6, phastCons 1 |
| Overall | ||
| CADD | 13.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0185%
Admixed American · 11/59,602 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.008%
Overall
0.00336%
54/1,607,004 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0185% | 5,418 |
| Middle Eastern | 0.0165% | 6,056 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,753 |
| European (non-Finnish) | 0.00306% | 32,642 |
| African / African-American | 0.00267% | 37,465 |
| Finnishnot grpmax-eligible | 0.00157% | 63,842 |
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.Leu389=
- Coding
- c.1167C>T
- MANE Select
- NM_002599
- dbSNP
- rs149180422
- Type
- single nucleotide variant
- Location
- chr11:72586085 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.17 · 44 PDB
- Residue 389
- an α-helix
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-leu389 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown