PDE3A p.Ile951=
c.2853C>A · VCV3609258
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00518%, 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 0.39 | GERP -1.4, phastCons 0.99 |
| Overall | ||
| CADD | 4.979 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00518%
European (non-Finnish) · 61/1,177,486 alleles
Filtering AF
0.00411%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00372%
Overall
0.0041%
66/1,610,830 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00518% | 19,303 |
| Admixed American | 0.00333% | 29,985 |
| African / African-American | 0.00267% | 37,416 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,374 |
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.Ile951=
- Coding
- c.2853C>A
- MANE Select
- NM_000921
- Type
- single nucleotide variant
- Location
- chr12:20650528 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.11 · 9 PDB
- Residue 951
- the 'interaction with slfn12' region; 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-ile951 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown