Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Common
common (popmax 79.8%, mid) — too common for a highly-penetrant pathogenic allele
Conditions
1
hypogonadotropic hypogonadism 3 with or without anosmia
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 -6.1 | GERP -3.7 |
| Overall | ||
| CADD | 0.325 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
79.8%
Middle Eastern · 4,834/6,060 alleles
Filtering AF
77.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 77.1%
Overall
74.9%
1,208,121/1,613,922 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 79.8% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 79.2% | 1 |
| South Asian | 77.2% | 1 |
| Finnishnot grpmax-eligible | 76.2% | 1 |
| European (non-Finnish) | 75.2% | 1 |
| Remaining individualsnot grpmax-eligible | 74.8% | 1 |
| Admixed American | 74.3% | 1 |
| African / African-American | 70.1% | 1 |
| East Asian | 64.1% | 2 |
| Amishnot grpmax-eligible | 60.2% | 2 |
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.Thr195=
- Coding
- c.585G>C
- MANE Select
- NM_144773
- dbSNP
- rs3746682
- Type
- single nucleotide variant
- Location
- chr20:5302610 (GRCh38)
- Gene constraint
- LOEUF 1.492 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50
- Residue 195
- a disulfide bond
Similar variants
- PROKR2 p.Thr195Met Uncertain significance ★ ⚠ same residue
- 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
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-thr195 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown