Is ROCK2 p.Gln863Pro (c.2588A>C) pathogenic?

ROCK2 p.Gln863Pro (c.2588A>C) is classified Uncertain significance in ROCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1; Associated with ROCK2-related disorder.

What condition is associated with ROCK2 p.Gln863Pro (c.2588A>C)?

ROCK2 p.Gln863Pro (c.2588A>C) is associated with ROCK2-related disorder (ClinVar).

How common is ROCK2 p.Gln863Pro (c.2588A>C) in the general population?

ROCK2 p.Gln863Pro (c.2588A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROCK2 p.Gln863Pro (c.2588A>C)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

ROCK2 p.Gln863Pro

c.2588A>C · rs2527785768 · VCV2632574

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ROCK2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic · top 7% in ROCK2
REVEL	0.501	indeterminate
SaProt	LLR -12.70	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 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 23 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	29.0	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

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: ROCK2
Protein: p.Gln863Pro
Coding: c.2588A>C
MANE Select: NM_004850
dbSNP: rs2527785768
Type: single nucleotide variant
Location: chr2:11202083 (GRCh38)
Gene constraint: LOEUF 0.346 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.79 · 23 PDB

Full ROCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ROCK2-related disorder

Similar variants

ROCK2 p.Ile944Phe Uncertain significance ★ ⚠ same condition
ROCK2 p.Thr793Ile Uncertain significance ⚠ same condition
ROCK2 c.1332+8G>T Likely benign same condition
ROCK2 c.1689+9A>C Likely benign same condition
ROCK2 c.2550-8C>G Likely benign same condition
ROCK2 c.2620-6A>G Benign same condition
ROCK2 c.3688-5C>T Likely benign same condition
ROCK2 p.Ala145= 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/rock2-p-gln863pro (accessed [today's date]).

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