Is ROR2 p.Arg522fs (c.1565_1569delinsTGTA) pathogenic?

ROR2 p.Arg522fs (c.15651569delinsTGTA) is classified Likely pathogenic in ROR2 (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Arg522fs (c.1565_1569delinsTGTA)?

ROR2 p.Arg522fs (c.1565_1569delinsTGTA) is associated with autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Arg522fs (c.1565_1569delinsTGTA) in the general population?

ROR2 p.Arg522fs (c.1565_1569delinsTGTA) is no gnomAD frequency available for this variant (gnomAD).

ROR2 p.Arg522fs

c.1565_1569delinsTGTA · rs1587655016 · VCV627538

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive Robinow syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.3	GERP -3.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ROR2
Protein: p.Arg522fs
Coding: c.1565_1569delinsTGTA
MANE Select: NM_004560
dbSNP: rs1587655016
Type: Indel
Location: chr9:91724925 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 522: the protein kinase domain; an α-helix

Full ROR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive Robinow syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ROR2 p.Arg522Trp Uncertain significance ★★ ⚠ same residue
ROR2 p.Arg522= Uncertain significance ★ same residue
ROR2 p.Arg522Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ROR2 p.Met291_Pro292delinsIleSer Uncertain significance ★ same condition
ROR2 c.175+1G>A Likely pathogenic ★★ same condition
ROR2 p.Arg119Ter Pathogenic ★★ same condition
ROR2 p.Arg397Ter Pathogenic ★★ same condition
ROR2 p.Arg442Ter Pathogenic ★★ 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/ror2-p-arg522fs (accessed [today's date]).

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