Is ROR2 p.Arg112Gln (c.335G>A) pathogenic?

ROR2 p.Arg112Gln (c.335G>A) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-09). AlphaMissense: likely benign (0.333); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Arg112Gln (c.335G>A)?

ROR2 p.Arg112Gln (c.335G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ROR2 p.Arg112Gln (c.335G>A) in the general population?

ROR2 p.Arg112Gln (c.335G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ROR2 p.Arg112Gln (c.335G>A)?

AlphaMissense predicts likely benign (score 0.333) — an in-silico prediction, not a clinical call.

ROR2 p.Arg112Gln

c.335G>A · rs780415376 · VCV2325040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.333	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,962 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,613,756 alleles · very rare exomes 6/1,461,890 · genomes 1/151,866 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,981
South Asian	0.0011%	91,048
European (non-Finnish)	0.000339%	294,997

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.Arg112Gln
Coding: c.335G>A
MANE Select: NM_004560
dbSNP: rs780415376
Type: single nucleotide variant
Location: chr9:91757400 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 112: 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.Arg112Trp 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
ROR2 p.Arg153Trp 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-arg112gln (accessed [today's date]).

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