Is GRHPR p.Val9= (c.27G>A) pathogenic?

GRHPR p.Val9= (c.27G>A) is classified Likely benign in GRHPR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-09). Very rare (popmax 0.00017%, nfe).

How common is GRHPR p.Val9= (c.27G>A) in the general population?

GRHPR p.Val9= (c.27G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

GRHPR p.Val9=

c.27G>A · rs1444931153 · VCV1104341

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.72	donor gain · deltas
Pangolin	Δ0.56	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,174,348 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000415% 6/1,446,778 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,781
Remaining individualsnot grpmax-eligible	0.00162%	61,726
European (non-Finnish)grpmax	0.00017%	587,175

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val9=
Coding: c.27G>A
MANE Select: NM_012203
dbSNP: rs1444931153
Type: single nucleotide variant
Location: chr9:37422777 (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 9: a β-strand

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

Similar variants

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
GRHPR c.865+1G>A Pathogenic/Likely 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-val9 (accessed [today's date]).

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