Is GRHPR p.Val31= (c.93G>A) pathogenic?

GRHPR p.Val31= (c.93G>A) is classified Likely benign in GRHPR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-01). Ultra-rare (popmax 0.0194%, nfe); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with GRHPR p.Val31= (c.93G>A)?

GRHPR p.Val31= (c.93G>A) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is GRHPR p.Val31= (c.93G>A) in the general population?

GRHPR p.Val31= (c.93G>A) is ultra-rare (popmax 0.0194%, nfe) (gnomAD).

GRHPR p.Val31=

c.93G>A · rs141330907 · VCV1106329

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, nfe)

Conditions

Nephrolithiasis/nephrocalcinosis

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 2.1	GERP -0.21, phastCons 1
Overall
CADD	12.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0194% European (non-Finnish) · 229/1,179,810 alleles

Filtering AF 0.0173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.0145% 234/1,613,124 alleles · ultra-rare exomes 227/1,460,876 · genomes 7/152,248 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0194%	5,152
Middle Eastern	0.0167%	5,992
Remaining individualsnot grpmax-eligible	0.00641%	15,611

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.Val31=
Coding: c.93G>A
MANE Select: NM_012203
dbSNP: rs141330907
Type: single nucleotide variant
Location: chr9:37424854 (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 31: a β-strand

Full GRHPR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Nephrolithiasis/nephrocalcinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRHPR p.Ala169Pro Uncertain significance ★★ ⚠ same condition
GRHPR p.Arg185Cys Uncertain significance ★★ ⚠ same condition
GRHPR p.Arg99Gln Uncertain significance ★★ ⚠ same condition
GRHPR p.Gly176Ser Uncertain significance ★★ ⚠ same condition
GRHPR p.Gly54Ser Uncertain significance ★★ ⚠ same condition
GRHPR p.Ile164Val Uncertain significance ★★ ⚠ same condition
GRHPR p.Ile263Thr Uncertain significance ★★ ⚠ same condition
GRHPR p.Ile40Thr 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/grhpr-p-val31 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown