Is ROR2 p.His562= (c.1686C>T) pathogenic?

ROR2 p.His562= (c.1686C>T) is classified Benign in ROR2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Common (popmax 7.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with brachydactyly type B1.

What condition is associated with ROR2 p.His562= (c.1686C>T)?

ROR2 p.His562= (c.1686C>T) is associated with brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

ROR2 p.His562=

Q: How common is ROR2 p.His562= (c.1686C>T) in the general population?

ROR2 p.His562= (c.1686C>T) is common (popmax 7.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1686C>T · rs56048121 · VCV281495

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 7.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

brachydactyly type B1

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 -3	GERP -3
Overall
CADD	2.642	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.9% East Asian · 3,534/44,750 alleles

Filtering AF 7.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.59%

Overall 0.273% 4,393/1,608,786 alleles · common exomes 3,865/1,456,446 · genomes 528/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	7.9%	13
Remaining individualsnot grpmax-eligible	0.628%	159
South Asian	0.261%	383
Middle Eastern	0.116%	863
African / African-American	0.0667%	1,499
Admixed American	0.0651%	1,536
Ashkenazi Jewishnot grpmax-eligible	0.0578%	1,730
European (non-Finnish)	0.01%	9,966

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.His562=
Coding: c.1686C>T
MANE Select: NM_004560
dbSNP: rs56048121
Type: single nucleotide variant
Location: chr9:91724808 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 562: the protein kinase domain; an α-helix

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

Disease context

brachydactyly type B1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive Robinow syndrome

Similar variants

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
ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same condition
ROR2 c.175+3G>T Uncertain significance ★★ same condition
ROR2 c.-102G>T Uncertain significance ★★ same condition
ROR2 c.*135G>T Uncertain significance ★★ 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-his562 (accessed [today's date]).

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