Is GRHPR p.Glu128= (c.384G>A) pathogenic?

GRHPR p.Glu128= (c.384G>A) is classified Likely benign in GRHPR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-12). Very rare (popmax 0.00731%, nfe); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with GRHPR p.Glu128= (c.384G>A)?

GRHPR p.Glu128= (c.384G>A) is associated with Nephrolithiasis/nephrocalcinosis, primary hyperoxaluria type 2 (ClinVar).

How common is GRHPR p.Glu128= (c.384G>A) in the general population?

GRHPR p.Glu128= (c.384G>A) is very rare (popmax 0.00731%, nfe) (gnomAD).

GRHPR p.Glu128=

c.384G>A · rs372351685 · VCV799838

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00731%, 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 0.86	GERP -3.8, phastCons 1
Overall
CADD	3.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00731% European (non-Finnish) · 86/1,176,084 alleles

Filtering AF 0.00606% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00559%

Overall 0.00572% 92/1,609,656 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00731%	13,675
Admixed American	0.005%	20,000
Remaining individualsnot grpmax-eligible	0.00321%	31,169
African / African-American	0.00134%	74,846

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.Glu128=
Coding: c.384G>A
MANE Select: NM_012203
dbSNP: rs372351685
Type: single nucleotide variant
Location: chr9:37426634 (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 128: an α-helix

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

Also linked: primary hyperoxaluria type 2

Similar variants

GRHPR c.404+5G>A Likely pathogenic ★★ same condition
GRHPR c.493+2T>A Pathogenic/Likely pathogenic ★★ same condition
GRHPR c.494-2A>G Pathogenic/Likely pathogenic ★★ same condition
GRHPR c.734+1G>A Pathogenic/Likely pathogenic ★★ same condition
GRHPR c.735-1G>A Pathogenic/Likely pathogenic ★★ same condition
GRHPR c.83+1G>C Pathogenic/Likely pathogenic ★★ same condition
GRHPR c.84-2A>G Pathogenic ★★ same condition
GRHPR c.865+1G>A Pathogenic/Likely pathogenic ★★ 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-glu128 (accessed [today's date]).

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