PRR12 p.Pro277=
c.831G>A · rs12462756 · VCV1326596
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 44.6%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -2.9 |
| Overall | ||
| CADD | 0.059 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
44.6%
African / African-American · 33,432/74,926 alleles
Filtering AF
44.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 44.1%
Overall
19.7%
317,334/1,608,952 alleles · common
exomes 277,286/1,456,794 · genomes 40,048/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 44.6% | 2 |
| Middle Eastern | 32.5% | 3 |
| South Asian | 31.1% | 3 |
| Admixed American | 26.6% | 4 |
| Amishnot grpmax-eligible | 23.2% | 4 |
| Remaining individualsnot grpmax-eligible | 20.9% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 18.9% | 5 |
| East Asian | 17.5% | 6 |
| European (non-Finnish) | 17.2% | 6 |
| Finnishnot grpmax-eligible | 13.1% | 8 |
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.Pro277=
- Coding
- c.831G>A
- MANE Select
- NM_020719
- dbSNP
- rs12462756
- Type
- single nucleotide variant
- Location
- chr19:49595166 (GRCh38)
- Gene constraint
- LOEUF 0.18 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.84
- Residue 277
- the 'disordered' region; a UniProt-annotated variant site (in noc1)
Similar variants
- 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
- PRR12 p.Arg1755Gln 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-pro277 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown