PDE6A p.Leu355=
c.1063C>T · rs780461144 · VCV1151275
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00679%, nfe)
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 6.4 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 13.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00679%
European (non-Finnish) · 80/1,177,804 alleles
Filtering AF
0.00556%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00515%
83/1,611,564 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00679% | 14,723 |
| African / African-American | 0.00267% | 37,424 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,412 |
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.Leu355=
- Coding
- c.1063C>T
- MANE Select
- NM_000440
- dbSNP
- rs780461144
- Type
- single nucleotide variant
- Location
- chr5:149907314 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.80
- Residue 355
- the gaf 2 domain
Similar variants
- 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
- PDE6A c.2027+2T>G 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-leu355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown