PDE6A p.Ile684=
c.2052C>T · rs772049478 · VCV1102049
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, amr)
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 -5.2 | |
| Overall | ||
| CADD | 4.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
Admixed American · 12/59,978 alleles
Filtering AF
0.0115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00898%
Overall
0.00254%
41/1,612,684 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.02% | 4,998 |
| African / African-American | 0.00801% | 12,479 |
| East Asian | 0.00446% | 22,439 |
| South Asian | 0.0022% | 45,523 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,432 |
| European (non-Finnish) | 0.00153% | 65,495 |
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.Ile684=
- Coding
- c.2052C>T
- MANE Select
- NM_000440
- dbSNP
- rs772049478
- Type
- single nucleotide variant
- Location
- chr5:149883512 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.80
- Residue 684
- the pdease 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-ile684 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown