Is ROR2 p.Asn822= (c.2466C>T) pathogenic?

ROR2 p.Asn822= (c.2466C>T) is classified Benign/Likely benign in ROR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-08). Low-frequency (popmax 1.03%, sas); Associated with brachydactyly type B1.

What condition is associated with ROR2 p.Asn822= (c.2466C>T)?

ROR2 p.Asn822= (c.2466C>T) is associated with brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Asn822= (c.2466C>T) in the general population?

ROR2 p.Asn822= (c.2466C>T) is low-frequency (popmax 1.03%, sas) (gnomAD).

ROR2 p.Asn822=

c.2466C>T · rs146432734 · VCV289430

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, sas)

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 -10	GERP -3.8
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.03% South Asian · 939/91,060 alleles

Filtering AF 0.976% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.954%

Overall 0.0687% 1,108/1,612,174 alleles · low-frequency exomes 1,045/1,459,856 · genomes 63/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.03%	97
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Middle Eastern	0.0165%	6,062
African / African-American	0.016%	6,254
European (non-Finnish)	0.00992%	10,084
Admixed American	0.005%	20,003
East Asian	0.00446%	22,432

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.Asn822=
Coding: c.2466C>T
MANE Select: NM_004560
dbSNP: rs146432734
Type: single nucleotide variant
Location: chr9:91724028 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB

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-asn822 (accessed [today's date]).

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