Is GRK1 p.Val331= (c.993C>A) pathogenic?

GRK1 p.Val331= (c.993C>A) is classified Uncertain significance in GRK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-01). Ultra-rare (popmax 0.0231%, afr); Associated with inherited retinal dystrophy.

What condition is associated with GRK1 p.Val331= (c.993C>A)?

GRK1 p.Val331= (c.993C>A) is associated with inherited retinal dystrophy (ClinVar).

How common is GRK1 p.Val331= (c.993C>A) in the general population?

GRK1 p.Val331= (c.993C>A) is ultra-rare (popmax 0.0231%, afr) (gnomAD).

GRK1 p.Val331=

c.993C>A · VCV3249558

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, afr)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP -2.3, phastCons 1
Overall
CADD	3.906	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% African / African-American · 13/56,160 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.00285% 20/700,754 alleles · ultra-rare exomes 4/551,056 · genomes 16/149,698 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0231%	4,320
Middle Eastern	0.0229%	4,360
Admixed American	0.00202%	49,510
European (non-Finnish)	0.0013%	76,821

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: GRK1
Protein: p.Val331=
Coding: c.993C>A
MANE Select: NM_002929
Type: single nucleotide variant
Location: chr13:113723081 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.04 · 1 PDB
Residue 331: the protein kinase domain

Full GRK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRK1 p.Val380Asp Pathogenic/Likely pathogenic ★★ same condition
GRK1 p.Gly213Ser Uncertain significance ★★ same condition
GRK1 p.Arg407Gln Conflicting classifications of pathogenicity ★ same condition
GRK1 p.Arg438Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
GRK1 p.Asp483Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
GRK1 p.Pro541Leu Uncertain significance ★ ⚠ same condition
GRK1 p.Ser536Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
GRK1 c.699+7A>G Likely benign ★ 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/grk1-p-val331 (accessed [today's date]).

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