PDE11A p.Ala451=
c.1353T>C · rs748169188 · VCV2651571
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.073 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -4.5 |
| Overall | ||
| CADD | 1.086 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,022 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000891%
13/1,458,844 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,011 |
| European (non-Finnish) | 0.000934% | 107,023 |
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.Ala451=
- Coding
- c.1353T>C
- MANE Select
- NM_016953
- dbSNP
- rs748169188
- Type
- single nucleotide variant
- Location
- chr2:177875873 (GRCh38)
- Gene constraint
- LOEUF 1.118 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.12
- Residue 451
- the gaf 2 domain
Similar variants
- 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
- PDE11A c.1576+26C>T Benign ★★ 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-ala451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown