Is ROR2 p.His162Arg (c.485A>G) pathogenic?

ROR2 p.His162Arg (c.485A>G) is classified Conflicting classifications of pathogenicity in ROR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0714%, sas); Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.His162Arg (c.485A>G)?

ROR2 p.His162Arg (c.485A>G) is associated with Inborn genetic diseases, brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.His162Arg (c.485A>G) in the general population?

ROR2 p.His162Arg (c.485A>G) is ultra-rare (popmax 0.0714%, sas) (gnomAD).

What do computational predictors say about ROR2 p.His162Arg (c.485A>G)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

ROR2 p.His162Arg

c.485A>G · rs569718323 · VCV1594654

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0714%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	18.59	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 0.0714% South Asian · 65/91,082 alleles

Filtering AF 0.0574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00458% 74/1,614,064 alleles · ultra-rare exomes 66/1,461,714 · genomes 8/152,350 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0714%	1,401
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.00017%	589,946

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.His162Arg
Coding: c.485A>G
MANE Select: NM_004560
dbSNP: rs569718323
Type: single nucleotide variant
Location: chr9:91756080 (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

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 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
ROR2 c.*135G>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-his162arg (accessed [today's date]).

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