PRKD1 p.Pro146=
c.438C>G · rs758826307 · VCV739667
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor loss, 27 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.65 | GERP 0.61, phastCons 1 |
| Overall | ||
| CADD | 8.461 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,902 alleles
Filtering AF
0.000554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.00025%
4/1,602,476 alleles · very rare
exomes 2/1,450,408 · genomes 2/152,068 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,951 |
| European (non-Finnish) | 0.000171% | 586,033 |
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
- PRKD1
- Protein
- p.Pro146=
- Coding
- c.438C>G
- MANE Select
- NM_002742
- dbSNP
- rs758826307
- Type
- single nucleotide variant
- Location
- chr14:29666174 (GRCh38)
- Gene constraint
- LOEUF 0.762 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.99
Similar variants
- PRKD1 p.Pro146Leu Uncertain significance ★ ⚠ same residue
- PRKD1 p.Ala529Thr Uncertain significance ★★ ⚠ same type
- PRKD1 p.Arg201Trp Uncertain significance ★★ same type
- PRKD1 p.Arg203Lys Uncertain significance ★★ ⚠ same type
- PRKD1 p.Arg740Gln Uncertain significance ★★ ⚠ same type
- PRKD1 p.Asn498Ser Uncertain significance ★★ ⚠ same type
- PRKD1 p.Gln115His Uncertain significance ★★ ⚠ same type
- PRKD1 p.Gly486Arg 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/prkd1-p-pro146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown