Is ROR2 p.His558= (c.1674C>T) pathogenic?

ROR2 p.His558= (c.1674C>T) is classified Likely benign in ROR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-26). Very rare (popmax 0.00534%, afr); Associated with ROR2-related disorder.

What condition is associated with ROR2 p.His558= (c.1674C>T)?

ROR2 p.His558= (c.1674C>T) is associated with ROR2-related disorder (ClinVar).

How common is ROR2 p.His558= (c.1674C>T) in the general population?

ROR2 p.His558= (c.1674C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

ROR2 p.His558=

c.1674C>T · rs566937186 · VCV3043281

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 -5.3	GERP -3.8
Overall
CADD	0.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,840 alleles

Filtering AF 0.00379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00346%

Overall 0.00411% 66/1,607,000 alleles · very rare exomes 64/1,454,762 · genomes 2/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,710
European (non-Finnish)	0.00485%	20,619
South Asian	0.00332%	30,108
East Asian	0.00223%	44,770
Remaining individualsnot grpmax-eligible	0.00161%	62,164

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.His558=
Coding: c.1674C>T
MANE Select: NM_004560
dbSNP: rs566937186
Type: single nucleotide variant
Location: chr9:91724820 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 558: 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-his558 (accessed [today's date]).

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