PRKCSH p.Pro347=
c.1041G>A · VCV4940782
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00387%, nfe)
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 0.74 | GERP -2.6, phastCons 0.98 |
| Overall | ||
| CADD | 9.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00387%
European (non-Finnish) · 45/1,163,464 alleles
Filtering AF
0.00295%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00263%
Overall
0.00304%
48/1,580,846 alleles · very rare
exomes 44/1,428,892 · genomes 4/151,954 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00387% | 25,855 |
| South Asian | 0.00232% | 43,161 |
| Remaining individualsnot grpmax-eligible | 0.00164% | 61,054 |
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
- PRKCSH
- Protein
- p.Pro347=
- Coding
- c.1041G>A
- MANE Select
- NM_001289104
- Type
- single nucleotide variant
- Location
- chr19:11447704 (GRCh38)
- Gene constraint
- LOEUF 0.699 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.33 · 2 PDB
- Residue 347
- a UniProt-annotated variant site (in pcld1); the 'disordered' region
Similar variants
- PRKCSH p.Pro347Leu Uncertain significance ★★ ⚠ same residue
- PRKCSH c.683+1G>A Likely pathogenic ★★ same type
- PRKCSH c.684-1G>A Likely pathogenic ★★ same type
- PRKCSH c.762+2T>C Likely pathogenic ★★ same type
- PRKCSH p.Glu429Ter Pathogenic/Likely pathogenic ★★ same type
- PRKCSH c.1286+4C>T Uncertain significance ★★ same type
- PRKCSH p.Arg121Cys Uncertain significance ★★ ⚠ same type
- PRKCSH p.Arg121His 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/prkcsh-p-pro347 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown