PROKR2 p.Ser130=
c.390C>T · rs144778137 · VCV338860
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
rare (popmax 0.126%, nfe)
Conditions
2
Inborn genetic diseases
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 -4.2 | GERP -4.2 |
| Overall | ||
| CADD | 1.328 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.126%
European (non-Finnish) · 1,481/1,180,034 alleles
Filtering AF
0.12%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.118%
Overall
0.0988%
1,595/1,614,092 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.126% | 797 |
| Remaining individualsnot grpmax-eligible | 0.072% | 1,389 |
| Admixed American | 0.0533% | 1,875 |
| African / African-American | 0.0254% | 3,943 |
| Finnishnot grpmax-eligible | 0.0187% | 5,337 |
| Middle Eastern | 0.0164% | 6,084 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00675% | 14,804 |
| East Asian | 0.00223% | 44,902 |
| South Asian | 0.0022% | 45,545 |
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
- PROKR2
- Protein
- p.Ser130=
- Coding
- c.390C>T
- MANE Select
- NM_144773
- dbSNP
- rs144778137
- Type
- single nucleotide variant
- Location
- chr20:5313980 (GRCh38)
- Gene constraint
- LOEUF 1.492 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50
- Residue 130
- a disulfide bond
Similar variants
- PROKR2 p.Arg164Gln Likely pathogenic ★★ same condition
- PROKR2 p.Glu231Lys Likely pathogenic ★★ ⚠ same condition
- PROKR2 p.Tyr316Ter Likely pathogenic ★★ same condition
- PROKR2 p.Ala103Val Uncertain significance ★★ ⚠ same condition
- PROKR2 p.Ala129Thr Uncertain significance ★★ ⚠ same condition
- PROKR2 p.Ala156Thr Uncertain significance ★★ same condition
- PROKR2 p.Arg135Cys Uncertain significance ★★ ⚠ same condition
- PROKR2 p.Arg248Trp Uncertain significance ★★ ⚠ same condition
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/prokr2-p-ser130 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown