Is ROR2 p.Pro718= (c.2154C>T) pathogenic?

ROR2 p.Pro718= (c.2154C>T) is classified Benign in ROR2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 14.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Pro718= (c.2154C>T)?

ROR2 p.Pro718= (c.2154C>T) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

ROR2 p.Pro718=

Q: How common is ROR2 p.Pro718= (c.2154C>T) in the general population?

ROR2 p.Pro718= (c.2154C>T) is common (popmax 14.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2154C>T · rs2230577 · VCV159816

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 14.1%, eas) — too common for a highly-penetrant pathogenic allele

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 -11	GERP -3.8
Overall
CADD	0.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.1% East Asian · 6,330/44,874 alleles

Filtering AF 13.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.7%

Overall 7.18% 115,909/1,613,426 alleles · common exomes 106,494/1,461,128 · genomes 9,415/152,298 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	14.1%	7
Admixed American	11.5%	9
South Asian	10.7%	9
Finnishnot grpmax-eligible	10.3%	10
Remaining individualsnot grpmax-eligible	7.53%	13
European (non-Finnish)	6.67%	15
Ashkenazi Jewishnot grpmax-eligible	5.6%	18
Middle Eastern	5.59%	18
Amishnot grpmax-eligible	5.26%	19
African / African-American	1.33%	75

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.Pro718=
Coding: c.2154C>T
MANE Select: NM_004560
dbSNP: rs2230577
Type: single nucleotide variant
Location: chr9:91724340 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 718: the protein kinase domain

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 p.Pro718Ser Uncertain significance ★ ⚠ same residue
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

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-pro718 (accessed [today's date]).

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