PDE6D p.Arg23=
c.67C>A · rs570163390 · VCV2693895
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, eas)
Conditions
1
Joubert syndrome 22
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.39 | acceptor loss, 30 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 9.8 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 14.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,868 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.0013%
21/1,610,672 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,639 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,593 |
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
- PDE6D
- Protein
- p.Arg23=
- Coding
- c.67C>A
- MANE Select
- NM_002601
- dbSNP
- rs570163390
- Type
- single nucleotide variant
- Location
- chr2:231739172 (GRCh38)
- Gene constraint
- LOEUF 1.027 · pLI 0.23 (gnomAD)
- Structure
- AlphaFold pLDDT 96.40 · 40 PDB
- Residue 23
- a β-strand
Similar variants
- PDE6D p.Arg23Trp Uncertain significance ★★ ⚠ same residue
- PDE6D p.Arg23Gln Uncertain significance ★ ⚠ same residue
- PDE6D p.Arg23fs Pathogenic ★ same residue
- PDE6D p.Arg75His Uncertain significance ★★ ⚠ same condition
- PDE6D c.140-3C>T Likely benign ★★ same condition
- PDE6D c.371+8A>C Benign/Likely benign ★★ same condition
- PDE6D c.50+11G>C Likely benign ★★ same condition
- PDE6D p.Ala58= Likely benign ★★ same condition
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/pde6d-p-arg23 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown