GRHPR p.Leu326=
c.978C>T · rs749583128 · VCV1150261
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0659%, sas)
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 1.4 | GERP -0.015, phastCons 1 |
| Overall | ||
| CADD | 8.497 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0659%
South Asian · 60/91,076 alleles
Filtering AF
0.0525%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0476%
Overall
0.0039%
63/1,614,044 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0659% | 1,518 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
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.Leu326=
- Coding
- c.978C>T
- MANE Select
- NM_012203
- dbSNP
- rs749583128
- Type
- single nucleotide variant
- Location
- chr9:37436773 (GRCh38)
- Gene constraint
- LOEUF 1.313 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.80 · 4 PDB
Similar variants
- 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
- GRHPR c.865+1G>A Pathogenic/Likely 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-leu326 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown