Is GRHPR p.Arg5Ter (c.13C>T) pathogenic?

GRHPR p.Arg5Ter (c.13C>T) is classified Pathogenic in GRHPR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Very rare (popmax 8.55e-05%, nfe).

How common is GRHPR p.Arg5Ter (c.13C>T) in the general population?

GRHPR p.Arg5Ter (c.13C>T) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

GRHPR p.Arg5Ter

c.13C>T · rs979727637 · VCV649477

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.85	GERP -2.5
Overall
CADD	35.0	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

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,169,838 alleles

Overall 6.95e-05% 1/1,437,884 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.Arg5Ter
Coding: c.13C>T
MANE Select: NM_012203
dbSNP: rs979727637
Type: single nucleotide variant
Location: chr9:37422763 (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

Similar variants

GRHPR p.Arg5Gln Uncertain significance ⚠ same residue
GRHPR c.404+5G>A Likely pathogenic ★★ same type
GRHPR c.493+2T>A Pathogenic/Likely pathogenic ★★ same type
GRHPR c.494-2A>G Pathogenic/Likely pathogenic ★★ same type
GRHPR c.734+1G>A Pathogenic/Likely pathogenic ★★ same type
GRHPR c.735-1G>A Pathogenic/Likely pathogenic ★★ same type
GRHPR c.83+1G>C Pathogenic/Likely pathogenic ★★ same type
GRHPR c.84-2A>G Pathogenic ★★ same type

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-arg5ter (accessed [today's date]).

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