Is ROR2 p.Arg107Trp (c.319C>T) pathogenic?

ROR2 p.Arg107Trp (c.319C>T) is classified Uncertain significance in ROR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-04). AlphaMissense: ambiguous (0.4055); Very rare (popmax 0.00834%, amr); Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Arg107Trp (c.319C>T)?

ROR2 p.Arg107Trp (c.319C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ROR2 p.Arg107Trp (c.319C>T) in the general population?

ROR2 p.Arg107Trp (c.319C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about ROR2 p.Arg107Trp (c.319C>T)?

AlphaMissense predicts ambiguous (score 0.4055) — an in-silico prediction, not a clinical call.

ROR2 p.Arg107Trp

c.319C>T · rs201740043 · VCV2387894

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4055	ambiguous
REVEL	0.44	indeterminate
SaProt	LLR -8.46	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP -1.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	23.1	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 0.00834% Admixed American · 5/59,962 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00248% 40/1,613,798 alleles · very rare exomes 30/1,461,888 · genomes 10/151,910 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,992
South Asian	0.00769%	13,006
African / African-American	0.00401%	24,956
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.00195%	51,304

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.Arg107Trp
Coding: c.319C>T
MANE Select: NM_004560
dbSNP: rs201740043
Type: single nucleotide variant
Location: chr9:91757416 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 107: 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.Arg153Trp Uncertain significance ★★ ⚠ same condition
ROR2 p.Arg178Gln Uncertain significance ★★ ⚠ same condition
ROR2 p.Arg244Pro 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-arg107trp (accessed [today's date]).

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