PDE3A p.Leu724=
c.2172C>G · rs138359943 · VCV1908930
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000606%, nfe)
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 -0.49 | GERP -0.92, phastCons 0.03 |
| Overall | ||
| CADD | 5.707 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000606%
European (non-Finnish) · 7/1,154,326 alleles
Filtering AF
0.000252%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000162%
Overall
0.000442%
7/1,584,998 alleles · very rare
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
- PDE3A
- Protein
- p.Leu724=
- Coding
- c.2172C>G
- MANE Select
- NM_000921
- dbSNP
- rs138359943
- Type
- single nucleotide variant
- Location
- chr12:20639878 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.11 · 9 PDB
- Residue 724
- the 'interaction with slfn12' region; an α-helix; the pdease domain
Similar variants
- PDE3A p.Arg268Lys Uncertain significance ★★ ⚠ same type
- PDE3A p.Arg424His Uncertain significance ★★ ⚠ same type
- PDE3A p.Glu648Val Uncertain significance ★★ ⚠ same type
- PDE3A p.Pro430Leu Uncertain significance ★★ ⚠ same type
- PDE3A p.Ser325Pro Uncertain significance ★★ ⚠ same type
- PDE3A p.Ser633Ile Uncertain significance ★★ ⚠ same type
- PDE3A p.Thr383Lys Uncertain significance ★★ ⚠ same type
- PDE3A p.Thr609Ser 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/pde3a-p-leu724 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown