Is ROR2 p.Pro101Ser (c.301C>T) pathogenic?

ROR2 p.Pro101Ser (c.301C>T) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely pathogenic (0.7453); Very rare (popmax 0.00167%, amr); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Pro101Ser (c.301C>T)?

ROR2 p.Pro101Ser (c.301C>T) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Pro101Ser (c.301C>T) in the general population?

ROR2 p.Pro101Ser (c.301C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ROR2 p.Pro101Ser (c.301C>T)?

AlphaMissense predicts likely pathogenic (score 0.7453) — an in-silico prediction, not a clinical call.

ROR2 p.Pro101Ser

c.301C>T · VCV3597788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7453 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive Robinow syndrome

Computational evidence

Protein change
AlphaMissense	0.7453	likely pathogenic
REVEL	0.516	indeterminate
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	29.3	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 0.00167% Admixed American · 1/59,968 alleles

Overall 6.2e-05% 1/1,613,750 alleles · very rare exomes 1/1,461,890 · genomes 0/151,860 · joint denominator

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.Pro101Ser
Coding: c.301C>T
MANE Select: NM_004560
Type: single nucleotide variant
Location: chr9:91757434 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 101: the ig-like c2-type domain

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.Pro101Leu 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-pro101ser (accessed [today's date]).

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