Is ROR2 p.Met452fs (c.1353_1360del) pathogenic?

ROR2 p.Met452fs (c.13531360del) is classified Pathogenic in ROR2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-08-04). Very rare (popmax 0.00439%, sas); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Met452fs (c.1353_1360del)?

ROR2 p.Met452fs (c.1353_1360del) is associated with autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Met452fs (c.1353_1360del) in the general population?

ROR2 p.Met452fs (c.1353_1360del) is very rare (popmax 0.00439%, sas) (gnomAD).

ROR2 p.Met452fs

c.1353_1360del · rs1365019676 · VCV1188826

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 within the last 50 nt of the penultimate exon (8 of 9, 26 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,032 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,612,868 alleles · very rare exomes 4/1,460,618 · genomes 0/152,250 · joint denominator

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: ROR2
Protein: p.Met452fs
Coding: c.1353_1360del
MANE Select: NM_004560
dbSNP: rs1365019676
Type: Deletion
Location: chr9:91726567 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB

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.Met452Thr Uncertain significance ★★ ⚠ same residue
ROR2 p.Arg619fs Likely pathogenic ★ same condition
ROR2 p.Arg785fs Likely pathogenic ★ same condition
ROR2 p.Gln380fs Likely pathogenic ★ same condition
ROR2 p.Thr331fs Pathogenic ★ same condition
ROR2 p.Met452Val Likely benign ★ same residue
ROR2 c.622+762_1184-1036del Pathogenic same condition
ROR2 p.Gln225fs 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-met452fs (accessed [today's date]).

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