ADCY3 p.Pro989=
c.2967C>T · rs139344556 · VCV3059126
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.124%, afr)
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 -5.1 | GERP -5.4 |
| Overall | ||
| CADD | 2.88 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.124%
African / African-American · 93/74,988 alleles
Filtering AF
0.104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0961%
Overall
0.00657%
106/1,613,966 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.124% | 806 |
| South Asian | 0.0022% | 45,529 |
| Admixed American | 0.00167% | 60,012 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,500 |
| Finnishnot grpmax-eligible | 0.00156% | 64,018 |
| European (non-Finnish) | 0.000678% | 147,495 |
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.Pro989=
- Coding
- c.2967C>T
- MANE Select
- NM_004036
- dbSNP
- rs139344556
- Type
- single nucleotide variant
- Location
- chr2:24822547 (GRCh38)
- Gene constraint
- LOEUF 0.695 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.86
- Residue 989
- a UniProt-annotated variant site (risk factor for obesity)
Similar variants
- ADCY3 p.Ala512Thr Uncertain significance ★★ ⚠ same type
- ADCY3 p.Ala553Val Uncertain significance ★★ ⚠ same type
- ADCY3 p.Ala97Val Uncertain significance ★★ ⚠ same type
- ADCY3 p.Arg1041His Uncertain significance ★★ ⚠ same type
- ADCY3 p.Arg259Cys Uncertain significance ★★ ⚠ same type
- ADCY3 p.Arg705Lys Uncertain significance ★★ ⚠ same type
- ADCY3 p.Asp474Asn Uncertain significance ★★ ⚠ same type
- ADCY3 p.Cys727Arg Uncertain significance ★★ ⚠ 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/adcy3-p-pro989 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown