PDE6B p.Pro299=
c.897G>A · rs576439366 · VCV2156514
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0334%, eas)
Conditions
1
Inborn genetic diseases
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 -14 | GERP -4.5 |
| Overall | ||
| CADD | 0.415 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0334%
East Asian · 15/44,888 alleles
Filtering AF
0.0206%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0166%
Overall
0.0018%
29/1,613,812 alleles · ultra-rare
exomes 26/1,461,482 · genomes 3/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0334% | 2,993 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| South Asian | 0.0022% | 45,539 |
| Admixed American | 0.00167% | 60,022 |
| African / African-American | 0.00133% | 75,062 |
| European (non-Finnish) | 0.000593% | 168,572 |
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.Pro299=
- Coding
- c.897G>A
- MANE Select
- NM_000283
- dbSNP
- rs576439366
- Type
- single nucleotide variant
- Location
- chr4:654124 (GRCh38)
- Gene constraint
- LOEUF 1.238 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.72
- Residue 299
- the gaf 2 domain
Similar variants
- PDE6B p.Pro299Leu Uncertain significance ★ ⚠ same residue
- PDE6B p.Ala19Ser Uncertain significance ★★ ⚠ same condition
- PDE6B p.Ala341Thr Uncertain significance ★★ ⚠ same condition
- PDE6B p.Ala34Thr Uncertain significance ★★ ⚠ same condition
- PDE6B p.Ala589Thr Uncertain significance ★★ ⚠ same condition
- PDE6B p.Ala809Val Uncertain significance ★★ ⚠ same condition
- PDE6B p.Ala845Glu Uncertain significance ★★ ⚠ same condition
- PDE6B p.Arg304Cys Uncertain significance ★★ ⚠ same condition
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-pro299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown