ADCY3 p.Pro548=
c.1644C>G · VCV3346862
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, mid)
Conditions
1
ADCY3-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.1 | GERP -4.5 |
| Overall | ||
| CADD | 0.065 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Middle Eastern · 1/5,466 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,613,242 alleles · ultra-rare
exomes 4/1,460,950 · genomes 0/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0183% | 5,466 |
| European (non-Finnish) | 0.000254% | 393,311 |
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
- ADCY3
- Protein
- p.Pro548=
- Coding
- c.1644C>G
- MANE Select
- NM_004036
- Type
- single nucleotide variant
- Location
- chr2:24836935 (GRCh38)
- Gene constraint
- LOEUF 0.695 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.86
- Residue 548
- the 'disordered' region
Disease context
ADCY3-related disorder
Similar variants
- ADCY3 p.Val195Met Uncertain significance ★★ ⚠ same condition
- ADCY3 c.2496-13C>T Uncertain significance ★ same condition
- ADCY3 p.Arg252Cys Uncertain significance ★ ⚠ same condition
- ADCY3 p.Arg564His Uncertain significance ★ ⚠ same condition
- ADCY3 p.Arg623Cys Uncertain significance ★ ⚠ same condition
- ADCY3 p.Glu346Lys Uncertain significance ★ ⚠ same condition
- ADCY3 p.Met461Ile Uncertain significance ★ ⚠ same condition
- ADCY3 p.Thr738Met 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/adcy3-p-pro548 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown