PROKR2 p.Thr374=
c.1122C>A · rs76469093 · VCV338851
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.81%, sas)
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 4.4 | GERP 0.94, phastCons 1 |
| Overall | ||
| CADD | 3.456 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.81%
South Asian · 2,557/91,058 alleles
Filtering AF
2.72%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.68%
Overall
0.258%
4,164/1,614,086 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.81% | 36 |
| East Asian | 2.54% | 39 |
| Remaining individualsnot grpmax-eligible | 0.381% | 263 |
| Middle Eastern | 0.0495% | 2,021 |
| European (non-Finnish) | 0.0177% | 5,646 |
| African / African-American | 0.0147% | 6,821 |
| Admixed American | 0.00833% | 12,004 |
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.Thr374=
- Coding
- c.1122C>A
- MANE Select
- NM_144773
- dbSNP
- rs76469093
- Type
- single nucleotide variant
- Location
- chr20:5302073 (GRCh38)
- Gene constraint
- LOEUF 1.492 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50
Similar variants
- PROKR2 p.Thr374Ala 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-thr374 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown