Is ROR2 p.Ala288= (c.864G>A) pathogenic?

ROR2 p.Ala288= (c.864G>A) is classified Conflicting classifications of pathogenicity in ROR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-17). Very rare (popmax 0.00712%, nfe); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Ala288= (c.864G>A)?

ROR2 p.Ala288= (c.864G>A) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Ala288= (c.864G>A) in the general population?

ROR2 p.Ala288= (c.864G>A) is very rare (popmax 0.00712%, nfe) (gnomAD).

ROR2 p.Ala288=

c.864G>A · rs142926399 · VCV367511

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00712%, nfe)

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 -6.4	GERP -3.8
Overall
CADD	10.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00712% European (non-Finnish) · 84/1,179,124 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00541%

Overall 0.00553% 89/1,610,670 alleles · very rare exomes 83/1,458,334 · genomes 6/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00712%	14,037
African / African-American	0.00267%	37,518
Remaining individualsnot grpmax-eligible	0.0016%	62,358
Finnishnot grpmax-eligible	0.0016%	62,678
South Asian	0.0011%	90,552

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.Ala288=
Coding: c.864G>A
MANE Select: NM_004560
dbSNP: rs142926399
Type: single nucleotide variant
Location: chr9:91733195 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 288: the fz domain; an α-helix

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.Ala288Val 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-ala288 (accessed [today's date]).

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