Is GRHPR p.Thr152fs (c.454dup) pathogenic?

GRHPR p.Thr152fs (c.454dup) is classified Pathogenic in GRHPR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-07). Very rare (popmax 0.00187%, nfe); Associated with GRHPR-related disorders.

What condition is associated with GRHPR p.Thr152fs (c.454dup)?

GRHPR p.Thr152fs (c.454dup) is associated with GRHPR-related disorders, primary hyperoxaluria type 2 (ClinVar).

How common is GRHPR p.Thr152fs (c.454dup) in the general population?

GRHPR p.Thr152fs (c.454dup) is very rare (popmax 0.00187%, nfe) (gnomAD).

GRHPR p.Thr152fs

c.454dup · rs771019056 · VCV371016

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Conditions

GRHPR-related disorders

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 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.82	GERP -0.12, phastCons 0.95
Overall
CADD	27.6	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

Grpmax group 0.00187% European (non-Finnish) · 22/1,179,486 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,612,110 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00187%	53,613
Remaining individualsnot grpmax-eligible	0.0016%	62,430

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.Thr152fs
Coding: c.454dup
MANE Select: NM_012203
dbSNP: rs771019056
Type: Duplication
Location: chr9:37428532 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.80 · 4 PDB

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

Disease context

GRHPR-related disorders

Also linked: primary hyperoxaluria type 2

Similar variants

GRHPR p.Ser260fs Likely pathogenic ★★ same condition
GRHPR p.Thr202fs Likely pathogenic ★★ same condition
GRHPR p.Val77fs Pathogenic/Likely pathogenic ★★ same condition
GRHPR p.Thr152= Likely benign ★★ same residue
GRHPR c.737dup Likely pathogenic ★ same condition
GRHPR p.Ala257fs Pathogenic ★ same condition
GRHPR p.Asn311fs Likely pathogenic ★ same condition
GRHPR p.Asp252fs 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-thr152fs (accessed [today's date]).

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