PDE10A p.Lys596=
c.1788A>G · rs142222153 · VCV1461408
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.165%, mid)
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 -0.34 | GERP -2.4, phastCons 0.26 |
| Overall | ||
| CADD | 4.907 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.165%
Middle Eastern · 10/6,062 alleles
Filtering AF
0.0895%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0681%
Overall
0.00639%
103/1,612,612 alleles · rare
exomes 93/1,460,318 · genomes 10/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.165% | 606 |
| South Asian | 0.0373% | 2,679 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,867 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| African / African-American | 0.004% | 25,014 |
| European (non-Finnish) | 0.0039% | 25,646 |
| Admixed American | 0.00167% | 60,020 |
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
- PDE10A
- Protein
- p.Lys596=
- Coding
- c.1788A>G
- MANE Select
- NM_001385079
- dbSNP
- rs142222153
- Type
- single nucleotide variant
- Location
- chr6:165418643 (GRCh38)
- Gene constraint
- LOEUF 0.427 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.05 · 359 PDB
- Residue 596
- the gaf 2 domain
Similar variants
- PDE10A p.Phe566Leu Likely pathogenic ★★ same type
- PDE10A p.Phe600Cys Pathogenic/Likely pathogenic ★★ same type
- PDE10A p.Phe600Leu Pathogenic ★★ same type
- PDE10A p.Ala1052Ser Uncertain significance ★★ ⚠ same type
- PDE10A p.Asn502Ser Uncertain significance ★★ ⚠ same type
- PDE10A p.Asn559Ser Uncertain significance ★★ ⚠ same type
- PDE10A p.Asp307Glu Uncertain significance ★★ same type
- PDE10A p.Cys284Gly 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/pde10a-p-lys596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown