Is ROCK2 p.Asp601Val (c.1802A>T) pathogenic?

ROCK2 p.Asp601Val (c.1802A>T) is classified Conflicting classifications of pathogenicity in ROCK2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.2558); Ultra-rare (popmax 0.0693%, nfe); Associated with volvulus of midgut.

What condition is associated with ROCK2 p.Asp601Val (c.1802A>T)?

ROCK2 p.Asp601Val (c.1802A>T) is associated with volvulus of midgut (ClinVar).

How common is ROCK2 p.Asp601Val (c.1802A>T) in the general population?

ROCK2 p.Asp601Val (c.1802A>T) is ultra-rare (popmax 0.0693%, nfe) (gnomAD).

What do computational predictors say about ROCK2 p.Asp601Val (c.1802A>T)?

AlphaMissense predicts likely benign (score 0.2558) — an in-silico prediction, not a clinical call.

ROCK2 p.Asp601Val

c.1802A>T · rs35768389 · VCV1686313

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2558 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0693%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

volvulus of midgut

Computational evidence

Protein change
AlphaMissense	0.2558	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -7.88	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 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 23 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0693% European (non-Finnish) · 818/1,180,010 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0638%

Overall 0.0529% 853/1,613,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0693%	1,443
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.00934%	10,702
Finnishnot grpmax-eligible	0.00469%	21,339
Admixed American	0.00167%	60,006

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.Asp601Val
Coding: c.1802A>T
MANE Select: NM_004850
dbSNP: rs35768389
Type: single nucleotide variant
Location: chr2:11214974 (GRCh38)
Gene constraint: LOEUF 0.346 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.79 · 23 PDB
Residue 601: a UniProt-annotated variant site (in); the 'interaction with ppp1r12a' region

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

Disease context

volvulus of midgut — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ROCK2 c.3609-11A>C Benign ★★ same type
ROCK2 p.Thr431Asn Benign ★★ same type
ROCK2 p.Ala1013Thr Uncertain significance ★ ⚠ same type
ROCK2 p.Ala1018Thr Uncertain significance ★ ⚠ same type
ROCK2 p.Ala663Thr Uncertain significance ★ ⚠ same type
ROCK2 p.Ala663Val Uncertain significance ★ ⚠ same type
ROCK2 p.Arg1044Ter Uncertain significance ★ same type
ROCK2 p.Arg1050His 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/rock2-p-asp601val (accessed [today's date]).

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