Is ROR2 p.Gln225Pro (c.674A>C) pathogenic?

ROR2 p.Gln225Pro (c.674A>C) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: ambiguous (0.418); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Gln225Pro (c.674A>C)?

ROR2 p.Gln225Pro (c.674A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ROR2 p.Gln225Pro (c.674A>C) in the general population?

ROR2 p.Gln225Pro (c.674A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROR2 p.Gln225Pro (c.674A>C)?

AlphaMissense predicts ambiguous (score 0.418) — an in-silico prediction, not a clinical call.

ROR2 p.Gln225Pro

c.674A>C · VCV3947182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.418 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.418	ambiguous
REVEL	0.547	indeterminate
SaProt	LLR -9.78	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ROR2
Protein: p.Gln225Pro
Coding: c.674A>C
MANE Select: NM_004560
Type: single nucleotide variant
Location: chr9:91733385 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 225: an α-helix; the fz 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.Gln225Glu Uncertain significance ★ ⚠ same residue
ROR2 p.Gln225Arg Uncertain significance ★ ⚠ same residue
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

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-gln225pro (accessed [today's date]).

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