PDE8B p.Pro788=
c.2364C>G · VCV4738646
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -0.9 |
| Overall | ||
| CADD | 6.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,010 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000372%
6/1,614,078 alleles · very rare
exomes 3/1,461,866 · genomes 3/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,003 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 8.47e-05% | 1,180,048 |
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
- PDE8B
- Protein
- p.Pro788=
- Coding
- c.2364C>G
- MANE Select
- NM_003719
- Type
- single nucleotide variant
- Location
- chr5:77421934 (GRCh38)
- Gene constraint
- LOEUF 0.351 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.88
- Residue 788
- the pdease domain
Similar variants
- PDE8B c.*498C>A Uncertain significance ★★ same type
- PDE8B p.Ala232Ser Uncertain significance ★★ ⚠ same type
- PDE8B p.Ala4Val Uncertain significance ★★ ⚠ same type
- PDE8B p.Ala65Pro Uncertain significance ★★ ⚠ same type
- PDE8B p.Ala70Ser Uncertain significance ★★ ⚠ same type
- PDE8B p.Ala86Thr Uncertain significance ★★ ⚠ same type
- PDE8B p.Arg237Lys Uncertain significance ★★ ⚠ same type
- PDE8B p.Arg483Trp 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/pde8b-p-pro788 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown