Is ROCK2 p.Ala145= (c.435C>T) pathogenic?

ROCK2 p.Ala145= (c.435C>T) is classified Benign in ROCK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Low-frequency (popmax 2.95%, eas); Associated with ROCK2-related disorder.

What condition is associated with ROCK2 p.Ala145= (c.435C>T)?

ROCK2 p.Ala145= (c.435C>T) is associated with ROCK2-related disorder (ClinVar).

How common is ROCK2 p.Ala145= (c.435C>T) in the general population?

ROCK2 p.Ala145= (c.435C>T) is low-frequency (popmax 2.95%, eas) (gnomAD).

ROCK2 p.Ala145=

c.435C>T · rs2230773 · VCV3039798

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.95%, eas)

Conditions

ROCK2-related disorder

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 1.5	GERP -0.59, phastCons 1
Overall
CADD	8.895	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.95% East Asian · 1,274/43,190 alleles

Filtering AF 2.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.76%

Overall 0.0936% 1,471/1,572,262 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.95%	34
Remaining individualsnot grpmax-eligible	0.191%	524
African / African-American	0.0489%	2,046
South Asian	0.0351%	2,846
Middle Eastern	0.0169%	5,926
Admixed American	0.0111%	9,011
European (non-Finnish)	0.00086%	116,220

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: ROCK2
Protein: p.Ala145=
Coding: c.435C>T
MANE Select: NM_004850
dbSNP: rs2230773
Type: single nucleotide variant
Location: chr2:11249688 (GRCh38)
Gene constraint: LOEUF 0.346 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.79 · 23 PDB
Residue 145: the protein kinase domain; an α-helix

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

Disease context

ROCK2-related disorder

Similar variants

ROCK2 p.Gln863Pro Uncertain significance ★ ⚠ same condition
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

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-ala145 (accessed [today's date]).

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