Is ROR2 p.Asn92= (c.276C>T) pathogenic?

ROR2 p.Asn92= (c.276C>T) is classified Benign/Likely benign in ROR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Asn92= (c.276C>T)?

ROR2 p.Asn92= (c.276C>T) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

ROR2 p.Asn92=

Q: How common is ROR2 p.Asn92= (c.276C>T) in the general population?

ROR2 p.Asn92= (c.276C>T) is common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.276C>T · rs56227711 · VCV367517

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal recessive Robinow syndrome

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 -8.6	GERP -5.4
Overall
CADD	1.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.2% African / African-American · 7,616/74,918 alleles

Filtering AF 9.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.9%

Overall 0.563% 9,084/1,613,870 alleles · common exomes 4,787/1,461,890 · genomes 4,297/151,980 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.2%	10
Remaining individualsnot grpmax-eligible	0.696%	144
Admixed American	0.678%	147
Middle Eastern	0.676%	148
East Asian	0.366%	274
South Asian	0.0758%	1,319
European (non-Finnish)	0.0297%	3,371
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804

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.Asn92=
Coding: c.276C>T
MANE Select: NM_004560
dbSNP: rs56227711
Type: single nucleotide variant
Location: chr9:91757459 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 92: the ig-like c2-type domain

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

Disease context

autosomal recessive Robinow syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachydactyly type B1

Similar variants

ROR2 c.175+1G>A Likely pathogenic ★★ same condition
ROR2 p.Arg119Ter Pathogenic ★★ same condition
ROR2 p.Arg397Ter Pathogenic ★★ same condition
ROR2 p.Arg442Ter Pathogenic ★★ same condition
ROR2 p.Arg528Ter Pathogenic/Likely pathogenic ★★ same condition
ROR2 c.175+3G>T Uncertain significance ★★ same condition
ROR2 c.-102G>T Uncertain significance ★★ same condition
ROR2 c.*135G>T 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-asn92 (accessed [today's date]).

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