Is GRHPR p.Cys288fs (c.863del) pathogenic?

GRHPR p.Cys288fs (c.863del) is classified Likely pathogenic in GRHPR (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-22). Absent from gnomAD; Associated with primary hyperoxaluria type 2.

What condition is associated with GRHPR p.Cys288fs (c.863del)?

GRHPR p.Cys288fs (c.863del) is associated with primary hyperoxaluria type 2 (ClinVar).

How common is GRHPR p.Cys288fs (c.863del) in the general population?

GRHPR p.Cys288fs (c.863del) is absent from gnomAD (gnomAD).

How is Primary hyperoxaluria inherited?

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

GRHPR p.Cys288fs

c.863del · rs1554748598 · VCV556976

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 2 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GRHPR
Protein: p.Cys288fs
Coding: c.863del
MANE Select: NM_012203
dbSNP: rs1554748598
Type: Deletion
Location: chr9:37432136 (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 288: a β-strand

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 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
GRHPR p.Gln232fs 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-cys288fs (accessed [today's date]).

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