Is GRHPR p.Ser117fs (c.348del) pathogenic?

GRHPR p.Ser117fs (c.348del) is classified Likely pathogenic in GRHPR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). Very rare (popmax 0.0011%, sas); Associated with primary hyperoxaluria type 2.

What condition is associated with GRHPR p.Ser117fs (c.348del)?

GRHPR p.Ser117fs (c.348del) is associated with primary hyperoxaluria type 2 (ClinVar).

How common is GRHPR p.Ser117fs (c.348del) in the general population?

GRHPR p.Ser117fs (c.348del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Primary hyperoxaluria inherited?

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

GRHPR p.Ser117fs

c.348del · rs755926095 · VCV2664417

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

primary hyperoxaluria type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.84e-05% 1/1,461,686 alleles · very rare

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.Ser117fs
Coding: c.348del
MANE Select: NM_012203
dbSNP: rs755926095
Type: Deletion
Location: chr9:37426598 (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 117: 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.Ser117Pro Uncertain significance ★ ⚠ same residue
GRHPR c.206_214+11del Likely pathogenic ★★ same condition
GRHPR c.735-2del Likely pathogenic ★★ same condition
GRHPR p.Ala197fs Pathogenic/Likely pathogenic ★★ same condition
GRHPR p.Ala206fs Pathogenic/Likely pathogenic ★★ same condition
GRHPR p.Ala52fs Pathogenic/Likely pathogenic ★★ same condition
GRHPR p.Asp35fs Pathogenic ★★ same condition
GRHPR p.Asp91fs 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-ser117fs (accessed [today's date]).

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