PRKAR1B p.Phe355=
c.1065C>T · rs28488947 · VCV1210096
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 17.6%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.089 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.7 | GERP -4.1 |
| Overall | ||
| CADD | 1.652 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
17.6%
East Asian · 7,823/44,416 alleles
Filtering AF
17.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 17.2%
Overall
1.03%
16,433/1,603,114 alleles · common
exomes 13,898/1,450,876 · genomes 2,535/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 17.6% | 6 |
| African / African-American | 2.97% | 34 |
| Middle Eastern | 1.97% | 51 |
| Remaining individualsnot grpmax-eligible | 1.54% | 65 |
| South Asian | 1.46% | 69 |
| Amishnot grpmax-eligible | 1.1% | 91 |
| Admixed American | 0.417% | 240 |
| Ashkenazi Jewishnot grpmax-eligible | 0.409% | 244 |
| European (non-Finnish) | 0.301% | 332 |
| Finnishnot grpmax-eligible | 0.152% | 660 |
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.Phe355=
- Coding
- c.1065C>T
- MANE Select
- NM_001164760
- dbSNP
- rs28488947
- Type
- single nucleotide variant
- Location
- chr7:550511 (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-phe355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown