PROKR2 p.Ile321=
c.963C>T · rs142257149 · VCV699964
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
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 -0.5 | GERP -1.1, phastCons 0.002 |
| Overall | ||
| CADD | 9.251 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,062 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0294%
Overall
0.00793%
128/1,614,192 alleles · ultra-rare
exomes 118/1,461,892 · genomes 10/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| African / African-American | 0.0413% | 2,421 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| European (non-Finnish) | 0.00534% | 18,731 |
| South Asian | 0.00439% | 22,767 |
| Admixed American | 0.00333% | 30,012 |
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.Ile321=
- Coding
- c.963C>T
- MANE Select
- NM_144773
- dbSNP
- rs142257149
- Type
- single nucleotide variant
- Location
- chr20:5302232 (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-ile321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown