Is ROR2 p.Ala600Thr (c.1798G>A) pathogenic?

ROR2 p.Ala600Thr (c.1798G>A) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). AlphaMissense: ambiguous (0.5362); Very rare (popmax 0.00668%, eas); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Ala600Thr (c.1798G>A)?

ROR2 p.Ala600Thr (c.1798G>A) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Ala600Thr (c.1798G>A) in the general population?

ROR2 p.Ala600Thr (c.1798G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about ROR2 p.Ala600Thr (c.1798G>A)?

AlphaMissense predicts ambiguous (score 0.5362) — an in-silico prediction, not a clinical call.

ROR2 p.Ala600Thr

c.1798G>A · VCV3597738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

autosomal recessive Robinow syndrome

Computational evidence

Protein change
AlphaMissense	0.5362	ambiguous
REVEL	0.751	pathogenic-leaning
SaProt	LLR -12.31	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	24.8	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 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00118% 19/1,614,112 alleles · very rare exomes 18/1,461,880 · genomes 1/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
European (non-Finnish)	0.00136%	73,754

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.Ala600Thr
Coding: c.1798G>A
MANE Select: NM_004560
Type: single nucleotide variant
Location: chr9:91724696 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 600: the protein kinase 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.Ala600Val Uncertain significance ★★ ⚠ same residue
ROR2 p.Ala600= 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

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-ala600thr (accessed [today's date]).

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