PROKR2 p.Val230=
c.690C>T · rs377074263 · VCV696415
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0571%, sas)
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 -1.7 | GERP -3.7 |
| Overall | ||
| CADD | 0.427 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0571%
South Asian · 52/91,082 alleles
Filtering AF
0.0447%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0403%
Overall
0.0178%
287/1,614,198 alleles · ultra-rare
exomes 263/1,461,890 · genomes 24/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0571% | 1,752 |
| European (non-Finnish) | 0.0186% | 5,364 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| Admixed American | 0.01% | 10,005 |
| Finnishnot grpmax-eligible | 0.00156% | 64,036 |
| African / African-American | 0.00133% | 75,040 |
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.Val230=
- Coding
- c.690C>T
- MANE Select
- NM_144773
- dbSNP
- rs377074263
- Type
- single nucleotide variant
- Location
- chr20:5302505 (GRCh38)
- Gene constraint
- LOEUF 1.492 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50
Similar variants
- PROKR2 p.Arg164Gln Likely pathogenic ★★ same type
- PROKR2 p.Glu231Lys Likely pathogenic ★★ ⚠ same type
- PROKR2 p.Tyr316Ter Likely pathogenic ★★ same type
- PROKR2 p.Ala103Val Uncertain significance ★★ ⚠ same type
- PROKR2 p.Ala129Thr Uncertain significance ★★ ⚠ same type
- PROKR2 p.Ala156Thr Uncertain significance ★★ same type
- PROKR2 p.Arg135Cys Uncertain significance ★★ ⚠ same type
- PROKR2 p.Arg248Trp 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/prokr2-p-val230 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown