PDE9A p.Pro75=
c.225G>A · rs78479041 · VCV2556745
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0441%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.09 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.9 | GERP 0.006, phastCons 0.005 |
| Overall | ||
| CADD | 13.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0441%
European (non-Finnish) · 520/1,178,716 alleles
Filtering AF
0.041%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0397%
Overall
0.0363%
586/1,612,634 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0441% | 2,267 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,313 |
| African / African-American | 0.0307% | 3,261 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.00769% | 13,002 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,800 |
| Admixed American | 0.00667% | 14,999 |
| Finnishnot grpmax-eligible | 0.00312% | 32,006 |
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
- PDE9A
- Protein
- p.Pro75=
- Coding
- c.225G>A
- MANE Select
- NM_002606
- dbSNP
- rs78479041
- Type
- single nucleotide variant
- Location
- chr21:42698974 (GRCh38)
- Gene constraint
- LOEUF 1.092 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.38 · 25 PDB
Similar variants
- PDE9A p.Ala394Thr Likely benign ★★ same type
- PDE9A p.Met560Arg Benign ★★ same type
- PDE9A p.Ala348Val Uncertain significance ★ ⚠ same type
- PDE9A p.Ala349Thr Uncertain significance ★ ⚠ same type
- PDE9A p.Ala372Val Uncertain significance ★ ⚠ same type
- PDE9A p.Ala387Pro Uncertain significance ★ ⚠ same type
- PDE9A p.Ala387Thr Uncertain significance ★ ⚠ same type
- PDE9A p.Ala559Thr 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/pde9a-p-pro75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown