PDE3A p.Phe916=
c.2748C>T · rs779932840 · VCV1940794
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.8 | GERP -3.9 |
| Overall | ||
| CADD | 0.746 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,008 alleles
Filtering AF
0.00348%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00239%
Overall
0.00124%
20/1,610,906 alleles · ultra-rare
exomes 15/1,459,578 · genomes 5/151,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,008 |
| African / African-American | 0.00804% | 12,435 |
| East Asian | 0.00223% | 44,810 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,362 |
| European (non-Finnish) | 0.000934% | 107,087 |
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.Phe916=
- Coding
- c.2748C>T
- MANE Select
- NM_000921
- dbSNP
- rs779932840
- Type
- single nucleotide variant
- Location
- chr12:20648870 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.11 · 9 PDB
- Residue 916
- the 'interaction with slfn12' region; the pdease domain; an α-helix
Similar variants
- PDE3A p.Phe916Ile Uncertain significance ★ same residue
- 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
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-phe916 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown