PDE4D p.Pro86=
c.258G>A · rs1013897220 · VCV796245
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0407%, eas)
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 -2.3 | GERP 1.6 |
| Overall | ||
| CADD | 8.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0407%
East Asian · 12/29,448 alleles
Filtering AF
0.0235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0184%
Overall
0.00097%
12/1,237,494 alleles · ultra-rare
exomes 8/1,088,770 · genomes 4/148,724 · joint denominator
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.Pro86=
- Coding
- c.258G>A
- MANE Select
- NM_001104631
- dbSNP
- rs1013897220
- Type
- single nucleotide variant
- Location
- chr5:59893365 (GRCh38)
- Gene constraint
- LOEUF 0.403 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.01 · 122 PDB
- Residue 86
- 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-pro86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown