Is ROR2 p.Pro570Leu (c.1709C>T) pathogenic?

ROR2 p.Pro570Leu (c.1709C>T) is classified Uncertain significance in ROR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.7117); Very rare (popmax 0.00834%, amr); Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Pro570Leu (c.1709C>T)?

ROR2 p.Pro570Leu (c.1709C>T) is associated with Inborn genetic diseases, brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Pro570Leu (c.1709C>T) in the general population?

ROR2 p.Pro570Leu (c.1709C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about ROR2 p.Pro570Leu (c.1709C>T)?

AlphaMissense predicts likely pathogenic (score 0.7117) — an in-silico prediction, not a clinical call.

ROR2 p.Pro570Leu

c.1709C>T · rs546802275 · VCV2205002

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7117 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7117	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -11.40	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,960 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000869% 14/1,611,592 alleles · very rare exomes 11/1,459,404 · genomes 3/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,992
Remaining individualsnot grpmax-eligible	0.0016%	62,388
African / African-American	0.00134%	74,906
European (non-Finnish)	0.000594%	168,304

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.Pro570Leu
Coding: c.1709C>T
MANE Select: NM_004560
dbSNP: rs546802275
Type: single nucleotide variant
Location: chr9:91724785 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 570: the protein kinase domain

Full ROR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachydactyly type B1 autosomal recessive Robinow syndrome

Similar variants

ROR2 p.Pro570= Benign/Likely benign ★★ 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-pro570leu (accessed [today's date]).

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