Is GRHPR p.Asp35fs (c.103del) pathogenic?

GRHPR p.Asp35fs (c.103del) is classified Pathogenic in GRHPR (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0661%, nfe); Associated with GRHPR-related disorders.

What condition is associated with GRHPR p.Asp35fs (c.103del)?

GRHPR p.Asp35fs (c.103del) is associated with GRHPR-related disorders, nephrocalcinosis, nephrolithiasis (ClinVar).

How common is GRHPR p.Asp35fs (c.103del) in the general population?

GRHPR p.Asp35fs (c.103del) is ultra-rare (popmax 0.0661%, nfe) (gnomAD).

GRHPR p.Asp35fs

c.103del · rs80356708 · VCV5636

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, 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 2 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
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 0.0661% European (non-Finnish) · 780/1,179,852 alleles

Filtering AF 0.0622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0607%

Overall 0.0497% 801/1,613,266 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0661%	1,513
Remaining individualsnot grpmax-eligible	0.024%	4,163
African / African-American	0.004%	24,978
Finnishnot grpmax-eligible	0.00315%	31,767
South Asian	0.0011%	91,076

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.Asp35fs
Coding: c.103del
MANE Select: NM_012203
dbSNP: rs80356708
Type: Deletion
Location: chr9:37424862 (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: nephrocalcinosis nephrolithiasis primary hyperoxaluria type 2

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.Asp91fs Pathogenic/Likely pathogenic ★★ same condition
GRHPR p.Gln232fs Pathogenic ★★ same condition
GRHPR p.His87fs 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-asp35fs (accessed [today's date]).

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