PRKD2 p.Pro442=
c.1326G>A · VCV3770818
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.13%, amr)
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 -11 | GERP -3.5 |
| Overall | ||
| CADD | 0.348 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.13%
Admixed American · 78/60,002 alleles
Filtering AF
0.107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0982%
Overall
0.00552%
89/1,613,530 alleles · rare
exomes 82/1,461,224 · genomes 7/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.13% | 769 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| African / African-American | 0.00133% | 75,044 |
| European (non-Finnish) | 0.000509% | 196,595 |
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
- PRKD2
- Protein
- p.Pro442=
- Coding
- c.1326G>A
- MANE Select
- NM_016457
- Type
- single nucleotide variant
- Location
- chr19:46694125 (GRCh38)
- Gene constraint
- LOEUF 0.381 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.85 · 4 PDB
- Residue 442
- the ph domain; a β-strand
Similar variants
- PKD2 p.Leu442Phe Uncertain significance ★★ same residue
- PKD2 p.Leu442Ter Pathogenic ★ same residue
- PKD2 p.Leu442fs Pathogenic same residue
- PKD2 c.1094+1G>A Pathogenic ★★ same type
- PKD2 c.1094+1G>C Pathogenic ★★ same type
- PKD2 c.1319+1G>A Pathogenic/Likely pathogenic ★★ same type
- PKD2 c.1320-2A>C Pathogenic/Likely pathogenic ★★ same type
- PKD2 c.1548+1G>A Pathogenic/Likely pathogenic ★★ 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/prkd2-p-pro442 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown