Is ROR2 p.Asp124= (c.372C>T) pathogenic?

ROR2 p.Asp124= (c.372C>T) is classified Benign/Likely benign in ROR2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Rare (popmax 0.47%, sas); Associated with brachydactyly type B1.

What condition is associated with ROR2 p.Asp124= (c.372C>T)?

ROR2 p.Asp124= (c.372C>T) is associated with brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Asp124= (c.372C>T) in the general population?

ROR2 p.Asp124= (c.372C>T) is rare (popmax 0.47%, sas) (gnomAD).

ROR2 p.Asp124=

c.372C>T · rs145568368 · VCV196393

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.47%, sas)

Conditions

brachydactyly type B1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -2.4, phastCons 0.96
Overall
CADD	5.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.47% South Asian · 428/91,052 alleles

Filtering AF 0.433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.419%

Overall 0.361% 5,832/1,613,978 alleles · rare exomes 5,469/1,461,894 · genomes 363/152,084 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.47%	213
European (non-Finnish)	0.425%	235
Remaining individualsnot grpmax-eligible	0.301%	332
Admixed American	0.173%	577
Middle Eastern	0.115%	866
African / African-American	0.0653%	1,530
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,974
Finnishnot grpmax-eligible	0.0406%	2,462

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.Asp124=
Coding: c.372C>T
MANE Select: NM_004560
dbSNP: rs145568368
Type: single nucleotide variant
Location: chr9:91757363 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 124: the ig-like c2-type domain

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 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-asp124 (accessed [today's date]).

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