PDE6C p.His89=
c.267C>T · rs376967510 · VCV1161391
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, 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 4.3 | GERP 0.18, phastCons 1 |
| Overall | ||
| CADD | 8.656 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/60,002 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00579%
Overall
0.00149%
24/1,613,932 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.015% | 6,667 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish) | 0.0011% | 90,768 |
| South Asian | 0.0011% | 91,088 |
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.His89=
- Coding
- c.267C>T
- MANE Select
- NM_006204
- dbSNP
- rs376967510
- Type
- single nucleotide variant
- Location
- chr10:93612992 (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 89
- the gaf 1 domain; an α-helix
Similar variants
- PDE6C p.His89Tyr Uncertain significance ★★ ⚠ same residue
- 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
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-his89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown