PRKAR1B p.Pro334=
c.1002C>A · VCV4894893
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.367%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.289 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -4.1 |
| Overall | ||
| CADD | 1.746 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.367%
African / African-American · 272/74,024 alleles
Filtering AF
0.332%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.318%
Overall
0.0208%
331/1,593,494 alleles · rare
exomes 165/1,441,268 · genomes 166/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.367% | 272 |
| Middle Eastern | 0.0537% | 1,861 |
| Remaining individualsnot grpmax-eligible | 0.0375% | 2,665 |
| Admixed American | 0.025% | 4,004 |
| European (non-Finnish) | 0.00162% | 61,681 |
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
- PRKAR1B
- Protein
- p.Pro334=
- Coding
- c.1002C>A
- MANE Select
- NM_001164760
- Type
- single nucleotide variant
- Location
- chr7:550574 (GRCh38)
- Gene constraint
- LOEUF 0.686 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.24 · 3 PDB
Similar variants
- PRKAR1B p.Arg335Trp Pathogenic/Likely pathogenic ★★ same type
- DNAAF5 p.Asp87Tyr Uncertain significance ★★ ⚠ same type
- DNAAF5 p.Cys138Gly Uncertain significance ★★ ⚠ same type
- DNAAF5 p.Glu8Ala Uncertain significance ★★ ⚠ same type
- DNAAF5 p.Gly150Arg Uncertain significance ★★ ⚠ same type
- DNAAF5 p.Val6Ala Uncertain significance ★★ ⚠ same type
- PRKAR1B p.Ala204Val Uncertain significance ★★ ⚠ same type
- PRKAR1B p.Ala6Thr 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/prkar1b-p-pro334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown