PDE6B p.Ser700=
c.2100C>T · rs756145629 · VCV1130369
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0245%, eas)
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 -4.5 |
| Overall | ||
| CADD | 10.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0245%
East Asian · 11/44,852 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.0023%
37/1,607,932 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0245% | 4,077 |
| South Asian | 0.0231% | 4,332 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,758 |
| European (non-Finnish) | 0.00017% | 587,434 |
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
- PDE6B
- Protein
- p.Ser700=
- Coding
- c.2100C>T
- MANE Select
- NM_000283
- dbSNP
- rs756145629
- Type
- single nucleotide variant
- Location
- chr4:664192 (GRCh38)
- Gene constraint
- LOEUF 1.238 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.72
- Residue 700
- the pdease domain
Similar variants
- PDE6B p.Ser700Phe Uncertain significance ★★ ⚠ same residue
- PDE6B p.Ser700Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- PDE6B p.Ser700_Leu701del Uncertain significance ★ same residue
- PDE6B c.1059+2T>G Likely pathogenic ★★ same type
- PDE6B c.1060-1G>T Pathogenic/Likely pathogenic ★★ same type
- PDE6B c.1107+1G>T Likely pathogenic ★★ same type
- PDE6B c.1107+3A>G Pathogenic/Likely pathogenic ★★ same type
- PDE6B c.1468-2A>G 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/pde6b-p-ser700 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown