PDE6A p.Pro181=
c.543C>T · rs1754133109 · VCV3027700
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, eas)
Conditions
1
inherited retinal dystrophy
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 1.3 | GERP -2.6, phastCons 1 |
| Overall | ||
| CADD | 7.466 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,874 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.00112%
18/1,613,996 alleles · ultra-rare
exomes 18/1,461,696 · genomes 0/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,640 |
| South Asian | 0.0011% | 91,082 |
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.Pro181=
- Coding
- c.543C>T
- MANE Select
- NM_000440
- dbSNP
- rs1754133109
- Type
- single nucleotide variant
- Location
- chr5:149934650 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.80
- Residue 181
- the gaf 1 domain
Similar variants
- PDE6A c.1407+1G>C Pathogenic/Likely pathogenic ★★ same condition
- PDE6A c.1926+1G>A Pathogenic ★★ same condition
- PDE6A c.627+2T>G Pathogenic ★★ same condition
- PDE6A c.998+1G>A Pathogenic ★★ same condition
- PDE6A p.Arg102His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PDE6A p.Arg236Ter Pathogenic/Likely pathogenic ★★ same condition
- PDE6A p.Arg257Ter Pathogenic/Likely pathogenic ★★ same condition
- PDE6A p.Arg562Trp Pathogenic/Likely 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-pro181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown