PROKR2 p.Thr335=
c.1005G>A · rs150381386 · VCV338853
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.553%, afr)
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 -20 | GERP -3.7 |
| Overall | ||
| CADD | 0.082 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.553%
African / African-American · 415/75,026 alleles
Filtering AF
0.509%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.492%
Overall
0.0407%
657/1,614,170 alleles · rare
exomes 386/1,461,892 · genomes 271/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.553% | 181 |
| Admixed American | 0.0566% | 1,765 |
| Remaining individualsnot grpmax-eligible | 0.0496% | 2,016 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.0147% | 6,821 |
| East Asian | 0.00223% | 44,882 |
| South Asian | 0.0022% | 45,539 |
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.Thr335=
- Coding
- c.1005G>A
- MANE Select
- NM_144773
- dbSNP
- rs150381386
- Type
- single nucleotide variant
- Location
- chr20:5302190 (GRCh38)
- Gene constraint
- LOEUF 1.492 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50
- Residue 335
- a UniProt-annotated variant site (in)
Similar variants
- PROKR2 p.Thr335Met 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-thr335 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown