Is GRK7 p.Pro185Ser (c.553C>T) pathogenic?

GRK7 p.Pro185Ser (c.553C>T) is classified Uncertain significance in GRK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). AlphaMissense: likely benign (0.1377); Absent from gnomAD v4.1.

How common is GRK7 p.Pro185Ser (c.553C>T) in the general population?

GRK7 p.Pro185Ser (c.553C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRK7 p.Pro185Ser (c.553C>T)?

AlphaMissense predicts likely benign (score 0.1377) — an in-silico prediction, not a clinical call.

GRK7 p.Pro185Ser

c.553C>T · rs1225198061 · VCV2624410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1377 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1377	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -9.25	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 1.6	GERP 2, phastCons 0.002
Regional constraint	o/e 0.91	unconstrained · MANE · 39 kb · p 0.017 · regional, not allelic
Overall
CADD	18.99	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRK7
Protein: p.Pro185Ser
Coding: c.553C>T
MANE Select: NM_139209
dbSNP: rs1225198061
Type: single nucleotide variant
Location: chr3:141778837 (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-pro185ser (accessed [today's date]).

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