Is GRHPR p.Thr152= (c.456G>A) pathogenic?

GRHPR p.Thr152= (c.456G>A) is classified Likely benign in GRHPR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-31). Very rare (popmax 0.00878%, sas); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with GRHPR p.Thr152= (c.456G>A)?

GRHPR p.Thr152= (c.456G>A) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is GRHPR p.Thr152= (c.456G>A) in the general population?

GRHPR p.Thr152= (c.456G>A) is very rare (popmax 0.00878%, sas) (gnomAD).

GRHPR p.Thr152=

c.456G>A · rs140612021 · VCV753527

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

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 -9.6	GERP -4.2
Overall
CADD	2.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,070 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00453% 73/1,611,778 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
European (non-Finnish)	0.005%	19,987
Remaining individualsnot grpmax-eligible	0.0048%	20,812
African / African-American	0.00267%	37,519
Finnishnot grpmax-eligible	0.0016%	62,504

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.Thr152=
Coding: c.456G>A
MANE Select: NM_012203
dbSNP: rs140612021
Type: single nucleotide variant
Location: chr9:37428535 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.80 · 4 PDB

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.Thr152Arg Uncertain significance ★ ⚠ same residue
GRHPR p.Thr152fs Pathogenic ★★ same residue
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

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-thr152 (accessed [today's date]).

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