Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.726%, mid)
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 4.3 | GERP -3.6, phastCons 1 |
| Overall | ||
| CADD | 8.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.726%
Middle Eastern · 43/5,920 alleles
Filtering AF
0.554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.494%
Overall
0.0952%
1,536/1,613,346 alleles · rare
exomes 1,360/1,461,024 · genomes 176/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.726% | 138 |
| Ashkenazi Jewishnot grpmax-eligible | 0.311% | 322 |
| South Asian | 0.187% | 536 |
| Remaining individualsnot grpmax-eligible | 0.181% | 553 |
| Admixed American | 0.153% | 652 |
| European (non-Finnish) | 0.086% | 1,163 |
| African / African-American | 0.0107% | 9,376 |
| Finnishnot grpmax-eligible | 0.00469% | 21,341 |
| East Asian | 0.00223% | 44,808 |
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.Arg809=
- Coding
- c.2425A>C
- MANE Select
- NM_006204
- dbSNP
- rs1051926
- Type
- single nucleotide variant
- Location
- chr10:93663085 (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 809
- an α-helix; a UniProt-annotated variant site (in achm5); the pdease domain
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 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
- PDE6C p.Arg29Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PDE6C p.Arg527Ter 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-arg809 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown