Is ROR2 p.Ser868= (c.2604C>T) pathogenic?

ROR2 p.Ser868= (c.2604C>T) is classified Likely benign in ROR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-20). Rare (popmax 0.247%, mid); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Ser868= (c.2604C>T)?

ROR2 p.Ser868= (c.2604C>T) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Ser868= (c.2604C>T) in the general population?

ROR2 p.Ser868= (c.2604C>T) is rare (popmax 0.247%, mid) (gnomAD).

ROR2 p.Ser868=

c.2604C>T · rs369150056 · VCV1595374

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.247%, mid)

Conditions

autosomal recessive Robinow syndrome

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 -3.8, phastCons 1
Overall
CADD	2.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% Middle Eastern · 15/6,084 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00706% 114/1,613,892 alleles · rare exomes 104/1,461,684 · genomes 10/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.247%	406
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
South Asian	0.0406%	2,462
Remaining individualsnot grpmax-eligible	0.0112%	8,926
East Asian	0.00446%	22,446
European (non-Finnish)	0.00153%	65,557

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.Ser868=
Coding: c.2604C>T
MANE Select: NM_004560
dbSNP: rs369150056
Type: single nucleotide variant
Location: chr9:91723890 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 868: the 'disordered' region

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

Also linked: brachydactyly type B1

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-ser868 (accessed [today's date]).

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