Is ROR2 p.Arg10Gln (c.29G>A) pathogenic?

ROR2 p.Arg10Gln (c.29G>A) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: ambiguous (0.3511); Very rare (popmax 0.00262%, eas).

How common is ROR2 p.Arg10Gln (c.29G>A) in the general population?

ROR2 p.Arg10Gln (c.29G>A) is very rare (popmax 0.00262%, eas) (gnomAD).

What do computational predictors say about ROR2 p.Arg10Gln (c.29G>A)?

AlphaMissense predicts ambiguous (score 0.3511) — an in-silico prediction, not a clinical call.

ROR2 p.Arg10Gln

c.29G>A · VCV3635824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3511 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00262%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3511	ambiguous
REVEL	0.285	benign-leaning
SaProt	LLR -8.69	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -1.3
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	1.754	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 0.00262% East Asian · 1/38,136 alleles

Overall 0.000132% 2/1,516,946 alleles · very rare exomes 2/1,364,880 · genomes 0/152,066 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00262%	38,136
European (non-Finnish)	8.81e-05%	1,135,295

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.Arg10Gln
Coding: c.29G>A
MANE Select: NM_004560
Type: single nucleotide variant
Location: chr9:91949935 (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

Similar variants

ROR2 c.175+1G>A Likely pathogenic ★★ same type
ROR2 p.Arg119Ter Pathogenic ★★ same type
ROR2 p.Arg397Ter Pathogenic ★★ same type
ROR2 p.Arg442Ter Pathogenic ★★ same type
ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same type
ROR2 c.175+3G>T Uncertain significance ★★ same type
ROR2 c.-102G>T Uncertain significance ★★ same type
ROR2 c.*135G>T Uncertain significance ★★ same type

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-arg10gln (accessed [today's date]).

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