PDE6A p.Val166Ala
c.497T>C · rs199887926 · VCV845477
Computational evidence
| Protein change | ||
| AlphaMissense | 0.264 | likely benign |
|---|---|---|
| REVEL | 0.205 | benign-leaning |
| SaProt | LLR -9.02 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 77 kb · p 0.94 · regional, not allelic |
| Overall | ||
| CADD | 22.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0439% | 2,278 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,674 |
| Finnishnot grpmax-eligible | 0.00625% | 16,009 |
| Admixed American | 0.005% | 20,004 |
| African / African-American | 0.00267% | 37,474 |
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
- PDE6A
- Protein
- p.Val166Ala
- Coding
- c.497T>C
- MANE Select
- NM_000440
- dbSNP
- rs199887926
- Type
- single nucleotide variant
- Location
- chr5:149934696 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.80
- Residue 166
- the gaf 1 domain
Similar variants
- PDE6A p.Val166= Conflicting classifications of pathogenicity ★ same residue
- PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same condition
- PDE6A c.1407+1G>C Pathogenic/Likely pathogenic ★★ same condition
- PDE6A c.1620+1G>A Pathogenic ★★ same condition
- PDE6A c.1926+1G>A Pathogenic ★★ same condition
- PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ same condition
- PDE6A c.627+2T>G Pathogenic ★★ same condition
- PDE6A c.998+1G>A Pathogenic ★★ 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/pde6a-p-val166ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown