Is ROR2 p.Arg3Trp (c.7C>T) pathogenic?

ROR2 p.Arg3Trp (c.7C>T) is classified Benign/Likely benign in ROR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-10). AlphaMissense: likely pathogenic (0.581); Rare (popmax 0.886%, afr); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Arg3Trp (c.7C>T)?

ROR2 p.Arg3Trp (c.7C>T) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Arg3Trp (c.7C>T) in the general population?

ROR2 p.Arg3Trp (c.7C>T) is rare (popmax 0.886%, afr) (gnomAD).

What do computational predictors say about ROR2 p.Arg3Trp (c.7C>T)?

AlphaMissense predicts likely pathogenic (score 0.581) — an in-silico prediction, not a clinical call.

ROR2 p.Arg3Trp

c.7C>T · rs539329891 · VCV193287

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.581 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.886%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive Robinow syndrome

Computational evidence

Protein change
AlphaMissense	0.581	likely pathogenic
REVEL	0.267	benign-leaning
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.23, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	19.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.886% African / African-American · 594/67,076 alleles

Filtering AF 0.827% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.803%

Overall 0.0458% 676/1,477,256 alleles · rare exomes 302/1,325,254 · genomes 374/152,002 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.886%	113
Admixed American	0.0869%	1,151
Remaining individualsnot grpmax-eligible	0.0566%	1,768
Middle Eastern	0.0233%	4,300
European (non-Finnish)	0.00134%	74,726

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.Arg3Trp
Coding: c.7C>T
MANE Select: NM_004560
dbSNP: rs539329891
Type: single nucleotide variant
Location: chr9:91949957 (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

autosomal recessive Robinow syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachydactyly type B1

Similar variants

ROR2 p.Arg3Gln Uncertain significance ★ ⚠ same residue
ROR2 p.Arg3Leu 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

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-arg3trp (accessed [today's date]).

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