GRHPR p.Thr12=
c.36C>T · rs765256070 · VCV1149751
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0875%, 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 -1.3 | GERP -4.2 |
| Overall | ||
| CADD | 10.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0875%
Middle Eastern · 4/4,570 alleles
Filtering AF
0.0299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0179%
Overall
0.00225%
36/1,600,520 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0875% | 1,142 |
| European (non-Finnish) | 0.00264% | 37,907 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,752 |
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
- GRHPR
- Protein
- p.Thr12=
- Coding
- c.36C>T
- MANE Select
- NM_012203
- dbSNP
- rs765256070
- Type
- single nucleotide variant
- Location
- chr9:37422786 (GRCh38)
- Gene constraint
- LOEUF 1.313 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.80 · 4 PDB
- Residue 12
- a β-strand
Similar variants
- GRHPR p.Thr12Ala Uncertain significance ★ ⚠ same residue
- GRHPR c.404+5G>A Likely pathogenic ★★ same type
- GRHPR c.493+2T>A Pathogenic/Likely pathogenic ★★ same type
- GRHPR c.494-2A>G Pathogenic/Likely pathogenic ★★ same type
- GRHPR c.734+1G>A Pathogenic/Likely pathogenic ★★ same type
- GRHPR c.735-1G>A Pathogenic/Likely pathogenic ★★ same type
- GRHPR c.83+1G>C Pathogenic/Likely pathogenic ★★ same type
- GRHPR c.84-2A>G Pathogenic ★★ 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/grhpr-p-thr12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown