PDE11A p.Ala678=
c.2034G>A · rs78730670 · VCV738406
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.316%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.253 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -3.8 |
| Overall | ||
| CADD | 0.251 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.316%
Middle Eastern · 19/6,004 alleles
Filtering AF
0.207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.172%
Overall
0.025%
396/1,585,446 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.316% | 316 |
| Remaining individualsnot grpmax-eligible | 0.0487% | 2,052 |
| European (non-Finnish) | 0.0273% | 3,663 |
| Admixed American | 0.0183% | 5,450 |
| African / African-American | 0.0175% | 5,724 |
| South Asian | 0.00773% | 12,934 |
| Finnishnot grpmax-eligible | 0.00156% | 64,026 |
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
- PDE11A
- Protein
- p.Ala678=
- Coding
- c.2034G>A
- MANE Select
- NM_016953
- dbSNP
- rs78730670
- Type
- single nucleotide variant
- Location
- chr2:177727667 (GRCh38)
- Gene constraint
- LOEUF 1.118 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.12
- Residue 678
- the pdease domain
Similar variants
- PDE11A p.Ala678Thr Benign same residue
- PDE11A p.Ser604Ter Pathogenic/Likely pathogenic ★★ same type
- PDE11A p.Arg329Ter Uncertain significance ★★ same type
- PDE11A p.Arg867Trp Uncertain significance ★★ ⚠ same type
- PDE11A p.Gln374Ter Uncertain significance ★★ same type
- PDE11A p.Pro165Thr Uncertain significance ★★ ⚠ same type
- PDE11A p.Pro893Gln Uncertain significance ★★ ⚠ same type
- PDE11A p.Tyr658Cys 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/pde11a-p-ala678 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown