Is ROR2 p.Leu634= (c.1902G>A) pathogenic?

ROR2 p.Leu634= (c.1902G>A) is classified Likely benign in ROR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-26). Very rare (popmax 0.000339%, nfe); Associated with ROR2-related disorder.

What condition is associated with ROR2 p.Leu634= (c.1902G>A)?

ROR2 p.Leu634= (c.1902G>A) is associated with ROR2-related disorder (ClinVar).

How common is ROR2 p.Leu634= (c.1902G>A) in the general population?

ROR2 p.Leu634= (c.1902G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

ROR2 p.Leu634=

c.1902G>A · VCV3353187

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

ROR2-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 1.4	GERP 0.87, phastCons 1
Overall
CADD	7.674	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,022 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,114 alleles · very rare exomes 4/1,461,884 · genomes 0/152,230 · 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.Leu634=
Coding: c.1902G>A
MANE Select: NM_004560
Type: single nucleotide variant
Location: chr9:91724592 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 634: the protein kinase domain

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

Disease context

ROR2-related disorder

Similar variants

ROR2 p.Arg242His Uncertain significance ★★ ⚠ same condition
ROR2 p.Pro878Ala Uncertain significance ★★ ⚠ same condition
ROR2 p.Ser882Cys Uncertain significance ★★ same condition
ROR2 p.Arg657His Conflicting classifications of pathogenicity ★ ⚠ same condition
ROR2 p.Gln898His Conflicting classifications of pathogenicity ★ ⚠ same condition
ROR2 p.Gln910Arg Uncertain significance ★ ⚠ same condition
ROR2 p.Pro810Leu Uncertain significance ★ ⚠ same condition
ROR2 p.Ser762Leu Conflicting classifications of pathogenicity ★ ⚠ 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-leu634 (accessed [today's date]).

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