PDE4A p.Pro325=
c.975T>C · rs1484885343 · VCV2681476
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000299%, nfe)
Conditions
1
EBV-positive nodal T- and NK-cell lymphoma
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.83 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.7 | GERP -4.1 |
| Overall | ||
| CADD | 0.033 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000299%
European (non-Finnish) · 3/1,003,496 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.2e-05%
Overall
0.000211%
3/1,418,988 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
- PDE4A
- Protein
- p.Pro325=
- Coding
- c.975T>C
- MANE Select
- NM_001111307
- dbSNP
- rs1484885343
- Type
- single nucleotide variant
- Location
- chr19:10457976 (GRCh38)
- Gene constraint
- LOEUF 0.434 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 65.87 · 5 PDB
- Residue 325
- the 'disordered' region
Disease context
EBV-positive nodal T- and NK-cell lymphoma
Similar variants
- PDE4A p.Ala590= Benign ★★ same type
- PDE4A p.Arg20= 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
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-pro325 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown