ADCY5 p.Pro399=
c.1197G>T · rs111864274 · VCV2892206
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00466%, nfe)
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 -13 | GERP -5.5 |
| Overall | ||
| CADD | 0.255 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00466%
European (non-Finnish) · 55/1,179,956 alleles
Filtering AF
0.00367%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00329%
Overall
0.00341%
55/1,613,814 alleles · very rare
exomes 50/1,461,704 · genomes 5/152,110 · joint denominator
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.Pro399=
- Coding
- c.1197G>T
- MANE Select
- NM_183357
- dbSNP
- rs111864274
- Type
- single nucleotide variant
- Location
- chr3:123352519 (GRCh38)
- Gene constraint
- LOEUF 0.326 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.91 · 2 PDB
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-pro399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown