Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 46.6%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
2
achromatopsia
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 -1.4 | GERP -4.1 |
| Overall | ||
| CADD | 6.629 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
46.6%
East Asian · 20,874/44,780 alleles
Filtering AF
46.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 45.9%
Overall
34%
545,153/1,603,472 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 46.6% | 2 |
| Amishnot grpmax-eligible | 43% | 2 |
| African / African-American | 42.9% | 2 |
| Admixed American | 39.4% | 3 |
| Remaining individualsnot grpmax-eligible | 35.2% | 3 |
| Middle Eastern | 33.3% | 3 |
| European (non-Finnish) | 33% | 3 |
| Finnishnot grpmax-eligible | 32.6% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 32.2% | 3 |
| South Asian | 30.6% | 3 |
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
- PDE6C
- Protein
- p.Ala366=
- Coding
- c.1098G>A
- MANE Select
- NM_006204
- dbSNP
- rs714550
- Type
- single nucleotide variant
- Location
- chr10:93629284 (GRCh38)
- Gene constraint
- LOEUF 0.976 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.53 · 7 PDB
- Residue 366
- a UniProt-annotated variant site (in achm5); the gaf 2 domain; an α-helix
Disease context
achromatopsia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: cone dystrophy 4
For Achromatopsia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- PDE6C p.Ala366Glu Uncertain significance ★ ⚠ same residue
- PDE6C p.Ala366Val Uncertain significance ★ ⚠ same residue
- PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PDE6C c.1269+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PDE6C c.2283+1G>T Pathogenic/Likely pathogenic ★★ same condition
- PDE6C c.939+5G>A Pathogenic/Likely pathogenic ★★ same condition
- PDE6C p.Arg238Ter Pathogenic/Likely pathogenic ★★ same condition
- PDE6C p.Arg259Ter 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/pde6c-p-ala366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown