Is GRK1 p.Ser30Phe (c.89C>T) pathogenic?

GRK1 p.Ser30Phe (c.89C>T) is classified Uncertain significance in GRK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1329); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with GRK1 p.Ser30Phe (c.89C>T)?

GRK1 p.Ser30Phe (c.89C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRK1 p.Ser30Phe (c.89C>T) in the general population?

GRK1 p.Ser30Phe (c.89C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about GRK1 p.Ser30Phe (c.89C>T)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

GRK1 p.Ser30Phe

c.89C>T · VCV3522814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 0.24
Regional constraint	o/e 1.05	unconstrained · MANE · 68 kb · p 0.22 · regional, not allelic
Overall
CADD	19.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,690 alleles

Overall 6.21e-05% 1/1,611,034 alleles · very rare exomes 1/1,458,720 · genomes 0/152,314 · joint denominator

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.Ser30Phe
Coding: c.89C>T
MANE Select: NM_002929
Type: single nucleotide variant
Location: chr13:113667475 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.04 · 1 PDB
Residue 30: the 'n-terminal' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRK1 p.Ala18Thr Uncertain significance ★★ ⚠ same condition
GRK1 p.Arg31Trp Uncertain significance ★★ same condition
GRK1 p.Arg51Cys Uncertain significance ★★ ⚠ same condition
GRK1 p.Asp262His Uncertain significance ★★ ⚠ same condition
GRK1 p.Gly144Trp Uncertain significance ★★ ⚠ same condition
GRK1 p.Gly213Ser Uncertain significance ★★ same condition
GRK1 p.Gly68Ser Uncertain significance ★★ ⚠ same condition
GRK1 p.Ile269Thr Uncertain significance ★★ ⚠ 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-ser30phe (accessed [today's date]).

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