Is GRHPR p.Val156= (c.468C>T) pathogenic?

GRHPR p.Val156= (c.468C>T) is classified Conflicting classifications of pathogenicity in GRHPR (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-18). Rare (popmax 0.314%, mid); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with GRHPR p.Val156= (c.468C>T)?

GRHPR p.Val156= (c.468C>T) is associated with Nephrolithiasis/nephrocalcinosis, primary hyperoxaluria type 2 (ClinVar).

How common is GRHPR p.Val156= (c.468C>T) in the general population?

GRHPR p.Val156= (c.468C>T) is rare (popmax 0.314%, mid) (gnomAD).

GRHPR p.Val156=

c.468C>T · rs142509393 · VCV366855

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.314%, mid)

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.5	GERP -4.2
Overall
CADD	1.168	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.314% Middle Eastern · 19/6,054 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.0356% 573/1,610,508 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.314%	319
South Asian	0.0648%	1,543
European (non-Finnish)	0.0386%	2,590
Remaining individualsnot grpmax-eligible	0.032%	3,121
Admixed American	0.0133%	7,503
African / African-American	0.012%	8,336
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
East Asian	0.00223%	44,880
Finnishnot grpmax-eligible	0.00162%	61,886

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.Val156=
Coding: c.468C>T
MANE Select: NM_012203
dbSNP: rs142509393
Type: single nucleotide variant
Location: chr9:37428547 (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 156: 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

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-val156 (accessed [today's date]).

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