PRKAR2B p.Ile396=
c.1188C>T · rs76484258 · VCV786743
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.68%, mid)
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 -0.34 | GERP -5.6, phastCons 0.002 |
| Overall | ||
| CADD | 8.721 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.68%
Middle Eastern · 102/6,062 alleles
Filtering AF
1.47%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.44%
Overall
0.501%
8,089/1,613,984 alleles · low-frequency
exomes 7,409/1,461,722 · genomes 680/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.68% | 59 |
| South Asian | 1.54% | 65 |
| Ashkenazi Jewishnot grpmax-eligible | 0.686% | 146 |
| Remaining individualsnot grpmax-eligible | 0.536% | 187 |
| Admixed American | 0.51% | 196 |
| European (non-Finnish) | 0.476% | 210 |
| African / African-American | 0.0946% | 1,057 |
| Finnishnot grpmax-eligible | 0.0843% | 1,186 |
| East Asian | 0.00669% | 14,957 |
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
- PRKAR2B
- Protein
- p.Ile396=
- Coding
- c.1188C>T
- MANE Select
- NM_002736
- dbSNP
- rs76484258
- Type
- single nucleotide variant
- Location
- chr7:107159513 (GRCh38)
- Gene constraint
- LOEUF 0.658 · pLI 0.54 (gnomAD)
- Structure
- AlphaFold pLDDT 79.37
- Residue 396
- a binding site
Similar variants
- PRKAR2B c.307+1G>A Uncertain significance ★ same type
- PRKAR2B p.Arg218His Uncertain significance ★ ⚠ same type
- PRKAR2B p.Asn143Tyr Uncertain significance ★ ⚠ same type
- PRKAR2B p.Asn229Asp Uncertain significance ★ ⚠ same type
- PRKAR2B p.Asn229Ser Uncertain significance ★ ⚠ same type
- PRKAR2B p.Asn75Ser Uncertain significance ★ ⚠ same type
- PRKAR2B p.Asp140His Uncertain significance ★ ⚠ same type
- PRKAR2B p.Cys344Tyr 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/prkar2b-p-ile396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown