Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 34.1%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
2
inherited retinal dystrophy
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 3.9 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 8.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
34.1%
African / African-American · 25,576/74,940 alleles
Filtering AF
33.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 33.6%
Overall
17.7%
285,240/1,613,916 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 34.1% | 3 |
| South Asian | 29.1% | 3 |
| Admixed American | 28.2% | 4 |
| East Asian | 22.8% | 4 |
| Remaining individualsnot grpmax-eligible | 18.1% | 6 |
| Ashkenazi Jewishnot grpmax-eligible | 17% | 6 |
| Middle Eastern | 15.4% | 6 |
| Finnishnot grpmax-eligible | 15.2% | 7 |
| European (non-Finnish) | 15.2% | 7 |
| Amishnot grpmax-eligible | 12.4% | 8 |
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
- PDE6A
- Protein
- p.Arg111=
- Coding
- c.331A>C
- MANE Select
- NM_000440
- dbSNP
- rs2277925
- Type
- single nucleotide variant
- Location
- chr5:149944343 (GRCh38)
- Gene constraint
- LOEUF 0.888 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.80
- Residue 111
- the gaf 1 domain
Similar variants
- PDE6A p.Arg111Lys Uncertain significance ★★ ⚠ same residue
- PDE6A p.Arg111Trp Uncertain significance ★ same residue
- PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same condition
- PDE6A c.1407+1G>C Pathogenic/Likely pathogenic ★★ same condition
- PDE6A c.1620+1G>A Pathogenic ★★ same condition
- PDE6A c.1926+1G>A Pathogenic ★★ same condition
- PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ same condition
- PDE6A c.627+2T>G Pathogenic ★★ 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/pde6a-p-arg111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown