PROKR2 p.Ser188=
c.564G>A · rs776913520 · VCV2977635
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.045%, 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 -8.4 | GERP -3.7 |
| Overall | ||
| CADD | 0.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.045%
Admixed American · 27/59,984 alleles
Filtering AF
0.0317%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0273%
Overall
0.00669%
108/1,613,982 alleles · ultra-rare
exomes 78/1,461,848 · genomes 30/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.045% | 2,222 |
| Finnishnot grpmax-eligible | 0.0203% | 4,925 |
| European (non-Finnish) | 0.00525% | 19,033 |
| South Asian | 0.00439% | 22,773 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
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.Ser188=
- Coding
- c.564G>A
- MANE Select
- NM_144773
- dbSNP
- rs776913520
- Type
- single nucleotide variant
- Location
- chr20:5302631 (GRCh38)
- Gene constraint
- LOEUF 1.492 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50
- Residue 188
- a UniProt-annotated variant site (in hh3)
Similar variants
- PROKR2 p.Ser188Leu Conflicting classifications of pathogenicity ★ same residue
- 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
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-ser188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown