PDE6D p.Asp136=
c.408C>T · rs547505745 · VCV771080
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, afr)
Conditions
1
Joubert syndrome 22
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 |
|---|---|---|
| Pangolin | Δ0.31 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.55 | GERP -2.5, phastCons 0.99 |
| Overall | ||
| CADD | 7.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
African / African-American · 12/74,992 alleles
Filtering AF
0.00921%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00721%
Overall
0.0018%
29/1,611,896 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.016% | 6,249 |
| East Asian | 0.0134% | 7,476 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,808 |
| South Asian | 0.0022% | 45,500 |
| Admixed American | 0.00167% | 59,984 |
| European (non-Finnish) | 0.000424% | 235,611 |
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.Asp136=
- Coding
- c.408C>T
- MANE Select
- NM_002601
- dbSNP
- rs547505745
- Type
- single nucleotide variant
- Location
- chr2:231732997 (GRCh38)
- Gene constraint
- LOEUF 1.027 · pLI 0.23 (gnomAD)
- Structure
- AlphaFold pLDDT 96.40 · 40 PDB
Similar variants
- PDE6D p.Asp136Asn Likely benign ★★ same residue
- PDE6D p.Arg23Trp Uncertain significance ★★ ⚠ same condition
- 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
- PDE6D p.Arg13= 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-asp136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown