Is ROR2 p.Arg429Gln (c.1286G>A) pathogenic?

ROR2 p.Arg429Gln (c.1286G>A) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-14). AlphaMissense: likely benign (0.2758); Very rare (popmax 0.00167%, amr).

How common is ROR2 p.Arg429Gln (c.1286G>A) in the general population?

ROR2 p.Arg429Gln (c.1286G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ROR2 p.Arg429Gln (c.1286G>A)?

AlphaMissense predicts likely benign (score 0.2758) — an in-silico prediction, not a clinical call.

ROR2 p.Arg429Gln

c.1286G>A · rs745922319 · VCV2996462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2758 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2758	likely benign
REVEL	0.702	pathogenic-leaning
SaProt	LLR -8.92	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	33.0	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 0.00167% Admixed American · 1/59,976 alleles

Overall 0.000124% 2/1,613,834 alleles · very rare exomes 1/1,461,852 · genomes 1/151,982 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,976
African / African-American	0.00134%	74,838

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.Arg429Gln
Coding: c.1286G>A
MANE Select: NM_004560
dbSNP: rs745922319
Type: single nucleotide variant
Location: chr9:91726641 (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 p.Arg429Trp Uncertain significance ★★ ⚠ same residue
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

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-arg429gln (accessed [today's date]).

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