PDE4A p.Arg20=
c.60G>C · rs78392044 · VCV768971
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.44%, afr)
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 2.5 | GERP 0.47, phastCons 1 |
| Overall | ||
| CADD | 8.452 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.44%
African / African-American · 1,787/73,122 alleles
Filtering AF
2.35%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.31%
Overall
0.161%
2,562/1,587,724 alleles · low-frequency
exomes 1,428/1,435,454 · genomes 1,134/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.44% | 41 |
| Middle Eastern | 1.08% | 92 |
| Remaining individualsnot grpmax-eligible | 0.316% | 317 |
| Admixed American | 0.308% | 324 |
| European (non-Finnish) | 0.0277% | 3,605 |
| South Asian | 0.00784% | 12,749 |
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
- PDE4A
- Protein
- p.Arg20=
- Coding
- c.60G>C
- MANE Select
- NM_001111307
- dbSNP
- rs78392044
- Type
- single nucleotide variant
- Location
- chr19:10420824 (GRCh38)
- Gene constraint
- LOEUF 0.434 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 65.87 · 5 PDB
- Residue 20
- the 'disordered' region
Similar variants
- PDE4A p.Ala590= Benign ★★ same type
- PDE4A p.Arg608= Benign ★★ same type
- PDE4A p.Glu732Gly Benign ★★ same type
- PDE4A p.Pro331Ser Benign/Likely benign ★★ same type
- PDE4A p.Ser279= Benign ★★ same type
- PDE4A c.620+2T>C Uncertain significance ★ same type
- PDE4A p.Ala428Thr Uncertain significance ★ ⚠ same type
- PDE4A p.Ala508Asp 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/pde4a-p-arg20 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown