Is ROR2 p.Ala472= (c.1416G>A) pathogenic?

ROR2 p.Ala472= (c.1416G>A) is classified Conflicting classifications of pathogenicity in ROR2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-02). Ultra-rare (popmax 0.0493%, mid); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Ala472= (c.1416G>A)?

ROR2 p.Ala472= (c.1416G>A) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Ala472= (c.1416G>A) in the general population?

ROR2 p.Ala472= (c.1416G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

ROR2 p.Ala472=

c.1416G>A · rs201064212 · VCV367506

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, 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 -20	GERP -3.5
Overall
CADD	0.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00638% 103/1,613,914 alleles · ultra-rare exomes 92/1,461,718 · genomes 11/152,196 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
African / African-American	0.00801%	12,490
European (non-Finnish)	0.00678%	14,751
East Asian	0.00668%	14,963
South Asian	0.00659%	15,181
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Finnishnot grpmax-eligible	0.00157%	63,862

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.Ala472=
Coding: c.1416G>A
MANE Select: NM_004560
dbSNP: rs201064212
Type: single nucleotide variant
Location: chr9:91725078 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 472: 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.Ala472Val 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-ala472 (accessed [today's date]).

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