Is ROR2 p.Phe185Leu (c.553T>C) pathogenic?

ROR2 p.Phe185Leu (c.553T>C) is classified Uncertain significance in ROR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-31). AlphaMissense: likely pathogenic (0.9277); Absent from gnomAD v4.1; Associated with Short stature.

What condition is associated with ROR2 p.Phe185Leu (c.553T>C)?

ROR2 p.Phe185Leu (c.553T>C) is associated with Short stature (ClinVar).

How common is ROR2 p.Phe185Leu (c.553T>C) in the general population?

ROR2 p.Phe185Leu (c.553T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ROR2 p.Phe185Leu (c.553T>C)?

AlphaMissense predicts likely pathogenic (score 0.9277) — an in-silico prediction, not a clinical call.

ROR2 p.Phe185Leu

c.553T>C · rs1825070299 · VCV1012277

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9277 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Short stature

Computational evidence

Protein change
AlphaMissense	0.9277	likely pathogenic
REVEL	0.447	indeterminate
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	23.8	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

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.Phe185Leu
Coding: c.553T>C
MANE Select: NM_004560
dbSNP: rs1825070299
Type: single nucleotide variant
Location: chr9:91737460 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 185: an α-helix; the fz domain

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

Disease context

Short stature — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ROR2 c.175+1G>A Likely pathogenic ★★ same type
ROR2 p.Arg119Ter Pathogenic ★★ same type
ROR2 p.Arg397Ter Pathogenic ★★ same type
ROR2 p.Arg442Ter Pathogenic ★★ same type
ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same type
ROR2 c.175+3G>T Uncertain significance ★★ same type
ROR2 c.-102G>T Uncertain significance ★★ same type
ROR2 c.*135G>T Uncertain significance ★★ same type

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-phe185leu (accessed [today's date]).

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