Is ROR2 p.Ser882Cys (c.2645C>G) pathogenic?

ROR2 p.Ser882Cys (c.2645C>G) is classified Uncertain significance in ROR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-24). AlphaMissense: ambiguous (0.3444); Very rare (popmax 0.00729%, nfe); Associated with ROR2-related disorder.

What condition is associated with ROR2 p.Ser882Cys (c.2645C>G)?

ROR2 p.Ser882Cys (c.2645C>G) is associated with ROR2-related disorder (ClinVar).

How common is ROR2 p.Ser882Cys (c.2645C>G) in the general population?

ROR2 p.Ser882Cys (c.2645C>G) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about ROR2 p.Ser882Cys (c.2645C>G)?

AlphaMissense predicts ambiguous (score 0.3444) — an in-silico prediction, not a clinical call.

ROR2 p.Ser882Cys

c.2645C>G · rs200296562 · VCV2427823

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3444 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Conditions

ROR2-related disorder

Computational evidence

Protein change
AlphaMissense	0.3444	ambiguous
REVEL	0.339	indeterminate
SaProt	LLR -9.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	23.3	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 0.00729% European (non-Finnish) · 86/1,180,038 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00533% 86/1,613,940 alleles · very rare exomes 80/1,461,736 · genomes 6/152,204 · joint denominator

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.Ser882Cys
Coding: c.2645C>G
MANE Select: NM_004560
dbSNP: rs200296562
Type: single nucleotide variant
Location: chr9:91723849 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 882: the 'disordered' region

Full ROR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ROR2-related disorder

Similar variants

ROR2 p.Arg242His Uncertain significance ★★ ⚠ same condition
ROR2 p.Pro878Ala Uncertain significance ★★ ⚠ same condition
ROR2 p.Arg657His Conflicting classifications of pathogenicity ★ ⚠ same condition
ROR2 p.Gln898His Conflicting classifications of pathogenicity ★ ⚠ same condition
ROR2 p.Gln910Arg Uncertain significance ★ ⚠ same condition
ROR2 p.Pro810Leu Uncertain significance ★ ⚠ same condition
ROR2 p.Ser762Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
ROR2 p.Asp254= Likely benign 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-ser882cys (accessed [today's date]).

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