Is ROR2 p.Tyr830Cys (c.2489A>G) pathogenic?

ROR2 p.Tyr830Cys (c.2489A>G) is classified Uncertain significance in ROR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-01-22). AlphaMissense: likely benign (0.1802); Rare (popmax 0.116%, mid); Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Tyr830Cys (c.2489A>G)?

ROR2 p.Tyr830Cys (c.2489A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ROR2 p.Tyr830Cys (c.2489A>G) in the general population?

ROR2 p.Tyr830Cys (c.2489A>G) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about ROR2 p.Tyr830Cys (c.2489A>G)?

AlphaMissense predicts likely benign (score 0.1802) — an in-silico prediction, not a clinical call.

ROR2 p.Tyr830Cys

c.2489A>G · rs775640546 · VCV289268

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1802 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1802	likely benign
REVEL	0.36	indeterminate
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	27.1	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 0.116% Middle Eastern · 7/6,060 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0031% 50/1,612,644 alleles · rare exomes 46/1,460,356 · genomes 4/152,288 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	866
Remaining individualsnot grpmax-eligible	0.0128%	7,810
South Asian	0.00549%	18,216
European (non-Finnish)	0.00246%	40,688
Admixed American	0.00167%	60,006

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.Tyr830Cys
Coding: c.2489A>G
MANE Select: NM_004560
dbSNP: rs775640546
Type: single nucleotide variant
Location: chr9:91724005 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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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
ROR2 p.Arg178Gln 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-tyr830cys (accessed [today's date]).

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