ADCY5 p.Pro46=
c.138C>T · rs1263344673 · VCV1560723
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00733%, sas)
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 -1.3 | GERP -1.7 |
| Overall | ||
| CADD | 11.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00733%
South Asian · 5/68,198 alleles
Filtering AF
0.00284%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00185%
Overall
0.000783%
11/1,405,670 alleles · very rare
exomes 11/1,253,512 · genomes 0/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00733% | 13,640 |
| Remaining individualsnot grpmax-eligible | 0.00189% | 52,972 |
| European (non-Finnish) | 0.000461% | 216,711 |
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
- ADCY5
- Protein
- p.Pro46=
- Coding
- c.138C>T
- MANE Select
- NM_183357
- dbSNP
- rs1263344673
- Type
- single nucleotide variant
- Location
- chr3:123448408 (GRCh38)
- Gene constraint
- LOEUF 0.326 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.91 · 2 PDB
- Residue 46
- the 'disordered' region
Similar variants
- ADCY5 c.2088+1G>A Pathogenic ★★ same type
- ADCY5 p.Ala726Thr Pathogenic ★★ ⚠ same type
- ADCY5 p.Arg1013Cys Pathogenic/Likely pathogenic ★★ same type
- ADCY5 p.Arg418Gln Pathogenic ★★ same type
- ADCY5 p.Arg418Trp Pathogenic ★★ same type
- ADCY5 p.Arg760Ter Pathogenic ★★ same type
- ADCY5 p.Asp1015Glu Likely pathogenic ★★ same type
- ADCY5 p.Ser421Ter 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/adcy5-p-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown