PRR12 p.Val593=
c.1779C>T · VCV4534461
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, 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 -0.37 | GERP -2.4, phastCons 0.033 |
| Overall | ||
| CADD | 1.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/60,000 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00131%
21/1,603,564 alleles · ultra-rare
exomes 18/1,451,308 · genomes 3/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,000 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,193 |
| European (non-Finnish) | 0.000763% | 131,087 |
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
- PRR12
- Protein
- p.Val593=
- Coding
- c.1779C>T
- MANE Select
- NM_020719
- Type
- single nucleotide variant
- Location
- chr19:49596114 (GRCh38)
- Gene constraint
- LOEUF 0.18 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.84
- Residue 593
- a UniProt-annotated variant site (in noc1)
Similar variants
- PRR12 p.Val593Gly Uncertain significance ★ ⚠ same residue
- PRR12 p.Arg1169Trp Likely pathogenic ★★ ⚠ same type
- PRR12 p.Arg1320Ter Pathogenic ★★ same type
- PRR12 p.Gln264Ter Pathogenic ★★ same type
- PRR12 p.Gln919Ter Pathogenic ★★ same type
- PRR12 p.Glu640Ter Pathogenic ★★ same type
- PRR12 p.Ala1190Ser Uncertain significance ★★ ⚠ same type
- PRR12 p.Ala82Gly 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/prr12-p-val593 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown