Is ROR2 p.Asp254= (c.762C>T) pathogenic?

ROR2 p.Asp254= (c.762C>T) is classified Likely benign in ROR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-05). Ultra-rare (popmax 0.012%, afr); Associated with ROR2-related disorder.

What condition is associated with ROR2 p.Asp254= (c.762C>T)?

ROR2 p.Asp254= (c.762C>T) is associated with ROR2-related disorder (ClinVar).

How common is ROR2 p.Asp254= (c.762C>T) in the general population?

ROR2 p.Asp254= (c.762C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

ROR2 p.Asp254=

c.762C>T · rs775610296 · VCV3053607

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

ROR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.25	GERP -3.3, phastCons 0.011
Overall
CADD	11.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,928 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00521% 84/1,612,734 alleles · ultra-rare exomes 74/1,460,506 · genomes 10/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,325
Remaining individualsnot grpmax-eligible	0.00801%	12,488
European (non-Finnish)	0.00551%	18,150
South Asian	0.0044%	22,741
Admixed American	0.00167%	59,942

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.Asp254=
Coding: c.762C>T
MANE Select: NM_004560
dbSNP: rs775610296
Type: single nucleotide variant
Location: chr9:91733297 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 254: the fz domain; an α-helix

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

Disease context

ROR2-related disorder

Similar variants

ROR2 p.Asp254Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
ROR2 p.Arg242His Uncertain significance ★★ ⚠ same condition
ROR2 p.Pro878Ala Uncertain significance ★★ ⚠ same condition
ROR2 p.Ser882Cys 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

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-asp254 (accessed [today's date]).

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