ADCY4 p.Pro508=
c.1524G>A · rs78654006 · VCV2644137
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.489%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.054 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.44 · evaluated, not missing |
| Pangolin | Δ0.44 | loss · gain 0.01 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -1, phastCons 1 |
| Overall | ||
| CADD | 20.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.489%
European (non-Finnish) · 5,767/1,179,408 alleles
Filtering AF
0.478%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.474%
Overall
0.392%
6,317/1,612,826 alleles · rare
exomes 5,956/1,460,712 · genomes 361/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.489% | 205 |
| Finnishnot grpmax-eligible | 0.322% | 311 |
| Remaining individualsnot grpmax-eligible | 0.258% | 388 |
| Ashkenazi Jewishnot grpmax-eligible | 0.258% | 388 |
| Admixed American | 0.0767% | 1,304 |
| African / African-American | 0.06% | 1,666 |
| South Asian | 0.0176% | 5,689 |
| Middle Eastern | 0.0166% | 6,028 |
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
- ADCY4
- Protein
- p.Pro508=
- Coding
- c.1524G>A
- MANE Select
- NM_001198568
- dbSNP
- rs78654006
- Type
- single nucleotide variant
- Location
- chr14:24329061 (GRCh38)
- Gene constraint
- LOEUF 1.089 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.03
Similar variants
- ADCY4 c.3082-4G>T Benign ★★ same type
- ADCY4 p.Ala1035Val Uncertain significance ★ ⚠ same type
- ADCY4 p.Ala241Ser Uncertain significance ★ ⚠ same type
- ADCY4 p.Ala286Pro Uncertain significance ★ ⚠ same type
- ADCY4 p.Ala401Ser Uncertain significance ★ ⚠ same type
- ADCY4 p.Ala421Ser Uncertain significance ★ ⚠ same type
- ADCY4 p.Ala421Val Uncertain significance ★ ⚠ same type
- ADCY4 p.Ala423Gly 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/adcy4-p-pro508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown