PDE6B p.Pro42=
c.126G>A · rs533513647 · VCV1597537
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, afr)
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 -0.07 | GERP -3.1 |
| Overall | ||
| CADD | 5.808 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/75,062 alleles
Filtering AF
0.0187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00626%
101/1,613,504 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,574 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| Admixed American | 0.00666% | 15,007 |
| European (non-Finnish) | 0.00508% | 19,666 |
| East Asian | 0.00223% | 44,874 |
| South Asian | 0.0022% | 45,542 |
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.Pro42=
- Coding
- c.126G>A
- MANE Select
- NM_000283
- dbSNP
- rs533513647
- Type
- single nucleotide variant
- Location
- chr4:625752 (GRCh38)
- Gene constraint
- LOEUF 1.238 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.72
Similar variants
- PDE6B p.Pro42Leu Uncertain significance ★★ ⚠ same residue
- PDE6B p.Pro42fs Likely pathogenic ★ 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
- PDE6B c.1832+1G>T 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-pro42 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown