PDE6B p.Ala765=
c.2295C>T · VCV3614819
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.072 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -4.5 |
| Overall | ||
| CADD | 6.995 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/75,022 alleles
Filtering AF
0.000442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000372%
6/1,613,090 alleles · very rare
exomes 6/1,460,780 · genomes 0/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,511 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
| European (non-Finnish) | 0.000254% | 393,103 |
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.Ala765=
- Coding
- c.2295C>T
- MANE Select
- NM_000283
- Type
- single nucleotide variant
- Location
- chr4:666557 (GRCh38)
- Gene constraint
- LOEUF 1.238 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.72
- Residue 765
- the pdease domain
Similar variants
- PDE6B p.Ala765Pro Conflicting classifications of pathogenicity ★ ⚠ 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
- PDE6B c.1921-1G>A 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-ala765 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown