PDE4D p.Pro72=
c.216G>A · rs1452281390 · VCV1946179
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00451%, afr)
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 -1.7 | GERP 1 |
| Overall | ||
| CADD | 8.356 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00451%
African / African-American · 3/66,588 alleles
Filtering AF
0.0012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000632%
Overall
0.000357%
5/1,399,856 alleles · very rare
exomes 5/1,251,882 · genomes 0/147,974 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00451% | 22,196 |
| Remaining individualsnot grpmax-eligible | 0.00189% | 52,782 |
| European (non-Finnish) | 9.37e-05% | 1,067,426 |
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
- PDE4D
- Protein
- p.Pro72=
- Coding
- c.216G>A
- MANE Select
- NM_001104631
- dbSNP
- rs1452281390
- Type
- single nucleotide variant
- Location
- chr5:59893407 (GRCh38)
- Gene constraint
- LOEUF 0.403 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.01 · 122 PDB
- Residue 72
- the 'disordered' region
Similar variants
- PDE4D p.Ile678Thr Pathogenic ★★ same type
- PDE4D p.Pro225Leu Pathogenic ★★ same type
- PDE4D c.*4886A>C Uncertain significance ★★ same type
- PDE4D p.Arg133Trp Uncertain significance ★★ ⚠ same type
- PDE4D p.Arg151Gly Uncertain significance ★★ ⚠ same type
- PDE4D p.Arg249Gln Uncertain significance ★★ ⚠ same type
- PDE4D p.Arg727Trp Uncertain significance ★★ ⚠ same type
- PDE4D p.Asn264Ser 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/pde4d-p-pro72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown