Is GRHPR p.Val248= (c.744C>T) pathogenic?

GRHPR p.Val248= (c.744C>T) is classified Likely benign in GRHPR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-13). Ultra-rare (popmax 0.0176%, sas); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with GRHPR p.Val248= (c.744C>T)?

GRHPR p.Val248= (c.744C>T) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is GRHPR p.Val248= (c.744C>T) in the general population?

GRHPR p.Val248= (c.744C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

GRHPR p.Val248=

c.744C>T · rs373541730 · VCV1079588

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, 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 0.021	GERP -4.2, phastCons 0.63
Overall
CADD	2.718	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,080 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.0013% 21/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,692
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000254%	393,326

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.Val248=
Coding: c.744C>T
MANE Select: NM_012203
dbSNP: rs373541730
Type: single nucleotide variant
Location: chr9:37432017 (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 248: 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

Similar variants

GRHPR p.Val248Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
GRHPR p.Val248Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val248 (accessed [today's date]).

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