PDE6C p.Thr229=
c.687C>G · rs146803497 · VCV758170
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.561%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.43 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.58 | GERP 0.17, phastCons 0.82 |
| Overall | ||
| CADD | 6.352 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.561%
Middle Eastern · 34/6,062 alleles
Filtering AF
0.412%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.361%
Overall
0.0107%
172/1,613,984 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.561% | 178 |
| Ashkenazi Jewishnot grpmax-eligible | 0.135% | 740 |
| Remaining individualsnot grpmax-eligible | 0.04% | 2,500 |
| South Asian | 0.0253% | 3,959 |
| European (non-Finnish) | 0.00407% | 24,581 |
| Admixed American | 0.00167% | 60,020 |
| African / African-American | 0.00133% | 75,018 |
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.Thr229=
- Coding
- c.687C>G
- MANE Select
- NM_006204
- dbSNP
- rs146803497
- Type
- single nucleotide variant
- Location
- chr10:93620944 (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 229
- an α-helix
Similar variants
- PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same type
- PDE6C c.1269+1G>A Pathogenic/Likely pathogenic ★★ same type
- PDE6C c.2283+1G>T Pathogenic/Likely pathogenic ★★ same type
- PDE6C c.481-1G>A Likely pathogenic ★★ same type
- PDE6C c.939+2T>G Pathogenic/Likely pathogenic ★★ same type
- PDE6C c.939+5G>A Pathogenic/Likely pathogenic ★★ same type
- PDE6C p.Arg104Trp Pathogenic/Likely pathogenic ★★ same type
- PDE6C p.Arg238Ter 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/pde6c-p-thr229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown