Is ROR2 p.Ser243Ala (c.727T>G) pathogenic?

ROR2 p.Ser243Ala (c.727T>G) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.0934); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Ser243Ala (c.727T>G)?

ROR2 p.Ser243Ala (c.727T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ROR2 p.Ser243Ala (c.727T>G) in the general population?

ROR2 p.Ser243Ala (c.727T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROR2 p.Ser243Ala (c.727T>G)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

ROR2 p.Ser243Ala

c.727T>G · rs2490184363 · VCV2287459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP -0.66, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	20.7	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

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.Ser243Ala
Coding: c.727T>G
MANE Select: NM_004560
dbSNP: rs2490184363
Type: single nucleotide variant
Location: chr9:91733332 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 243: 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.Ser243= Likely benign ★ 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-ser243ala (accessed [today's date]).

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