PRR12 p.Pro974=
c.2922C>G · VCV4943366
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0055%, 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 -0.61 | GERP -3.5, phastCons 0.017 |
| Overall | ||
| CADD | 2.981 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0055%
Admixed American · 3/54,572 alleles
Filtering AF
0.00146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000704%
Overall
0.00127%
20/1,573,196 alleles · very rare
exomes 18/1,421,026 · genomes 2/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0055% | 18,191 |
| Remaining individualsnot grpmax-eligible | 0.00328% | 30,456 |
| European (non-Finnish) | 0.00129% | 77,354 |
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.Pro974=
- Coding
- c.2922C>G
- MANE Select
- NM_020719
- Type
- single nucleotide variant
- Location
- chr19:49597257 (GRCh38)
- Gene constraint
- LOEUF 0.18 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.84
- Residue 974
- a UniProt-annotated variant site (in noc1); the 'disordered' region
Similar variants
- PRR12 p.Pro974Leu 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-pro974 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown