PDE6A p.Ala836=
c.2508A>T · rs893912674 · VCV1605696
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.70 | acceptor loss, 2 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -1.1 |
| Overall | ||
| CADD | 0.415 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/60,020 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00578%
Overall
0.000684%
10/1,461,664 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.015% | 6,669 |
| European (non-Finnish) | 8.48e-05% | 1,179,917 |
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.Ala836=
- Coding
- c.2508A>T
- MANE Select
- NM_000440
- dbSNP
- rs893912674
- Type
- single nucleotide variant
- Location
- chr5:149860970 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.80
- Residue 836
- the 'disordered' region
Similar variants
- PDE6A p.Ala836Pro Uncertain significance ★ ⚠ same residue
- PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same type
- PDE6A c.1263+1G>T Pathogenic/Likely pathogenic ★★ same type
- PDE6A c.1407+1G>C Pathogenic/Likely pathogenic ★★ same type
- PDE6A c.1620+1G>A Pathogenic ★★ same type
- PDE6A c.1620+2T>A Pathogenic/Likely pathogenic ★★ same type
- PDE6A c.1926+1G>A Pathogenic ★★ same type
- PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ 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/pde6a-p-ala836 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown