Is ROCK2 p.Ser724= (c.2172C>T) pathogenic?

ROCK2 p.Ser724= (c.2172C>T) is classified Likely benign in ROCK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-10-20). Ultra-rare (popmax 0.0591%, nfe); Associated with ROCK2-related disorder.

What condition is associated with ROCK2 p.Ser724= (c.2172C>T)?

ROCK2 p.Ser724= (c.2172C>T) is associated with ROCK2-related disorder (ClinVar).

How common is ROCK2 p.Ser724= (c.2172C>T) in the general population?

ROCK2 p.Ser724= (c.2172C>T) is ultra-rare (popmax 0.0591%, nfe) (gnomAD).

ROCK2 p.Ser724=

c.2172C>T · rs200234402 · VCV3050996

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0591%, nfe)

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 3.8	GERP 0.34, phastCons 1
Overall
CADD	9.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0591% European (non-Finnish) · 696/1,178,056 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.054%

Overall 0.0463% 745/1,609,142 alleles · ultra-rare exomes 697/1,456,952 · genomes 48/152,190 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
European (non-Finnish)grpmax	0.0591%	1,693
Remaining individualsnot grpmax-eligible	0.045%	2,224
Middle Eastern	0.0166%	6,038
African / African-American	0.0121%	8,297
Admixed American	0.0102%	9,840
Finnishnot grpmax-eligible	0.0047%	21,259
South Asian	0.00111%	90,168

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser724=
Coding: c.2172C>T
MANE Select: NM_004850
dbSNP: rs200234402
Type: single nucleotide variant
Location: chr2:11211712 (GRCh38)
Gene constraint: LOEUF 0.346 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.79 · 23 PDB
Residue 724: the 'required for interaction with foxm1 isoform 5 (foxm1d)' region; the 'interaction with ppp1r12a' region

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-ser724 (accessed [today's date]).

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