Is GRHPR p.Glu113Ter (c.337G>T) pathogenic?

GRHPR p.Glu113Ter (c.337G>T) is classified Pathogenic in GRHPR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-10-30). Absent from gnomAD v4.1; Associated with primary hyperoxaluria type 2.

What condition is associated with GRHPR p.Glu113Ter (c.337G>T)?

GRHPR p.Glu113Ter (c.337G>T) is associated with primary hyperoxaluria type 2 (ClinVar).

How common is GRHPR p.Glu113Ter (c.337G>T) in the general population?

GRHPR p.Glu113Ter (c.337G>T) is absent from gnomAD v4.1 (gnomAD).

How is Primary hyperoxaluria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GRHPR p.Glu113Ter

c.337G>T · rs180177307 · VCV371535

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary hyperoxaluria type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	Δ0.27	acceptor loss, 49 bp away · masked 0 · deltas
Pangolin	Δ0.24	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRHPR
Protein: p.Glu113Ter
Coding: c.337G>T
MANE Select: NM_012203
dbSNP: rs180177307
Type: single nucleotide variant
Location: chr9:37426587 (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 113: an α-helix

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

Disease context

primary hyperoxaluria type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary hyperoxaluria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Germany)

Similar variants

GRHPR p.Glu113Lys Likely pathogenic ★★ same residue
GRHPR p.Glu113fs Likely pathogenic ★ same residue
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

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-glu113ter (accessed [today's date]).

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