PRKCSH p.Arg271=
c.813C>T · rs746700714 · VCV2885124
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
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 -14 | GERP -4.2 |
| Overall | ||
| CADD | 0.321 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,916 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000496%
8/1,613,876 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,729 |
| South Asian | 0.0022% | 45,546 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 8.48e-05% | 1,179,902 |
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.Arg271=
- Coding
- c.813C>T
- MANE Select
- NM_001289104
- dbSNP
- rs746700714
- Type
- single nucleotide variant
- Location
- chr19:11447124 (GRCh38)
- Gene constraint
- LOEUF 0.699 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.33 · 2 PDB
- Residue 271
- the ef-hand 2 domain; a UniProt-annotated variant site (in pcld1)
Similar variants
- PRKCSH p.Arg271Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- PRKCSH p.Arg271His Conflicting classifications of pathogenicity ★ ⚠ 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
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-arg271 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown