Is ROR2 p.Gln75Arg (c.224A>G) pathogenic?

ROR2 p.Gln75Arg (c.224A>G) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: ambiguous (0.4319); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Gln75Arg (c.224A>G)?

ROR2 p.Gln75Arg (c.224A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ROR2 p.Gln75Arg (c.224A>G) in the general population?

ROR2 p.Gln75Arg (c.224A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ROR2 p.Gln75Arg (c.224A>G)?

AlphaMissense predicts ambiguous (score 0.4319) — an in-silico prediction, not a clinical call.

ROR2 p.Gln75Arg

c.224A>G · rs1235241103 · VCV3155729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4319 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4319	ambiguous
REVEL	0.264	benign-leaning
SaProt	LLR -6.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	23.4	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 0.00223% East Asian · 1/44,852 alleles

Overall 0.000124% 2/1,613,750 alleles · very rare exomes 1/1,461,892 · genomes 1/151,858 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,852
European (non-Finnish)	8.47e-05%	1,179,976

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.Gln75Arg
Coding: c.224A>G
MANE Select: NM_004560
dbSNP: rs1235241103
Type: single nucleotide variant
Location: chr9:91757511 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 75: the ig-like c2-type domain

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

Similar variants

ROR2 p.Ala241Val Uncertain significance ★★ ⚠ same condition
ROR2 p.Ala288Val Uncertain significance ★★ ⚠ same condition
ROR2 p.Ala513Val Uncertain significance ★★ ⚠ same condition
ROR2 p.Ala597Val Uncertain significance ★★ ⚠ same condition
ROR2 p.Ala601Thr Uncertain significance ★★ ⚠ same condition
ROR2 p.Arg107Trp Uncertain significance ★★ same condition
ROR2 p.Arg153Trp Uncertain significance ★★ ⚠ same condition
ROR2 p.Arg178Gln 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-gln75arg (accessed [today's date]).

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