PDE6C p.Val128=
c.384G>A · VCV4693384
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0296%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.40 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.5 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 15.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0296%
South Asian · 27/91,082 alleles
Filtering AF
0.0208%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.018%
Overall
0.00205%
30/1,461,860 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0296% | 3,373 |
| African / African-American | 0.00133% | 75,064 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Val128=
- Coding
- c.384G>A
- MANE Select
- NM_006204
- Type
- single nucleotide variant
- Location
- chr10:93613109 (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 128
- the gaf 1 domain
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-val128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown