Is ROR2 p.Lys285Arg (c.854A>G) pathogenic?

ROR2 p.Lys285Arg (c.854A>G) is classified Likely pathogenic in ROR2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0704); Ultra-rare (popmax 0.0264%, sas); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Lys285Arg (c.854A>G)?

ROR2 p.Lys285Arg (c.854A>G) is associated with autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Lys285Arg (c.854A>G) in the general population?

ROR2 p.Lys285Arg (c.854A>G) is ultra-rare (popmax 0.0264%, sas) (gnomAD).

What do computational predictors say about ROR2 p.Lys285Arg (c.854A>G)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

ROR2 p.Lys285Arg

c.854A>G · rs768848657 · VCV2502303

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive Robinow syndrome

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign ⚠ discordant with ClinVar
REVEL	0.238	benign-leaning
SaProt	LLR -4.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.29	donor gain · deltas
Constraint at this position
Conservation	phyloP 2.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	22.3	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 0.0264% South Asian · 24/90,746 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.00149% 24/1,611,664 alleles · ultra-rare exomes 21/1,459,518 · genomes 3/152,146 · 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.Lys285Arg
Coding: c.854A>G
MANE Select: NM_004560
dbSNP: rs768848657
Type: single nucleotide variant
Location: chr9:91733205 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 285: the fz 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

Similar variants

ROR2 p.Lys285Glu 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-lys285arg (accessed [today's date]).

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