Is GRHPR p.Ile212= (c.636C>T) pathogenic?

GRHPR p.Ile212= (c.636C>T) is classified Benign in GRHPR (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-25). Rare (popmax 0.236%, sas); Associated with primary hyperoxaluria type 2.

What condition is associated with GRHPR p.Ile212= (c.636C>T)?

GRHPR p.Ile212= (c.636C>T) is associated with primary hyperoxaluria type 2 (ClinVar).

How common is GRHPR p.Ile212= (c.636C>T) in the general population?

GRHPR p.Ile212= (c.636C>T) is rare (popmax 0.236%, sas) (gnomAD).

How is Primary hyperoxaluria inherited?

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

GRHPR p.Ile212=

c.636C>T · rs548848730 · VCV1170250

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.236%, sas)

Conditions

primary hyperoxaluria type 2

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 Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.8	GERP -3.7
Overall
CADD	2.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.236% South Asian · 215/91,076 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.2%

Overall 0.0144% 233/1,613,646 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.236%	424
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.016%	6,250
European (non-Finnish)	0.000509%	196,584

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.Ile212=
Coding: c.636C>T
MANE Select: NM_012203
dbSNP: rs548848730
Type: single nucleotide variant
Location: chr9:37430548 (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 212: 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.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-ile212 (accessed [today's date]).

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