Is ROR2 p.Asp166= (c.498T>C) pathogenic?

ROR2 p.Asp166= (c.498T>C) is classified Benign in ROR2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 17.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with brachydactyly type B1.

What condition is associated with ROR2 p.Asp166= (c.498T>C)?

ROR2 p.Asp166= (c.498T>C) is associated with brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

ROR2 p.Asp166=

Q: How common is ROR2 p.Asp166= (c.498T>C) in the general population?

ROR2 p.Asp166= (c.498T>C) is common (popmax 17.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.498T>C · rs16907720 · VCV159820

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 17.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

brachydactyly type B1

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 -5.9	GERP -5.6
Overall
CADD	0.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.3% African / African-American · 12,983/74,986 alleles

Filtering AF 17.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 17%

Overall 6.19% 99,835/1,614,098 alleles · common exomes 86,683/1,461,860 · genomes 13,152/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	17.3%	6
Middle Eastern	8.73%	11
Ashkenazi Jewishnot grpmax-eligible	7.24%	14
Remaining individualsnot grpmax-eligible	6.66%	15
European (non-Finnish)	6.18%	16
Amishnot grpmax-eligible	4.82%	21
Finnishnot grpmax-eligible	4.43%	23
Admixed American	4.41%	23
South Asian	1.72%	58
East Asian	0.00891%	11,223

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.Asp166=
Coding: c.498T>C
MANE Select: NM_004560
dbSNP: rs16907720
Type: single nucleotide variant
Location: chr9:91737515 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB

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

Disease context

brachydactyly type B1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive Robinow syndrome

Similar variants

ROR2 p.Asp166Tyr Uncertain significance ★ ⚠ same residue
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

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-asp166 (accessed [today's date]).

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