Is GRK7 p.Trp178Arg (c.532T>C) pathogenic?

GRK7 p.Trp178Arg (c.532T>C) is classified Uncertain significance in GRK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.9918); Very rare (popmax 0.00673%, amr).

How common is GRK7 p.Trp178Arg (c.532T>C) in the general population?

GRK7 p.Trp178Arg (c.532T>C) is very rare (popmax 0.00673%, amr) (gnomAD).

What do computational predictors say about GRK7 p.Trp178Arg (c.532T>C)?

AlphaMissense predicts likely pathogenic (score 0.9918) — an in-silico prediction, not a clinical call.

GRK7 p.Trp178Arg

c.532T>C · rs760942018 · VCV2462921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9918 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9918	likely pathogenic · top 5% in GRK7
REVEL	0.626	indeterminate
SaProt	LLR -12.94	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 39 kb · p 0.017 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00673% Admixed American · 4/59,478 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000274% 4/1,458,738 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: GRK7
Protein: p.Trp178Arg
Coding: c.532T>C
MANE Select: NM_139209
dbSNP: rs760942018
Type: single nucleotide variant
Location: chr3:141778816 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.79

Full GRK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRK7 p.Ala236Gly Uncertain significance ★ ⚠ same type
GRK7 p.Ala298Thr Uncertain significance ★ ⚠ same type
GRK7 p.Ala351Asp Uncertain significance ★ ⚠ same type
GRK7 p.Ala46Thr Uncertain significance ★ ⚠ same type
GRK7 p.Ala6Asp Uncertain significance ★ ⚠ same type
GRK7 p.Ala84Glu Uncertain significance ★ ⚠ same type
GRK7 p.Arg20Trp Uncertain significance ★ ⚠ same type
GRK7 p.Arg286His Uncertain significance ★ ⚠ 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/grk7-p-trp178arg (accessed [today's date]).

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