Is ROR2 p.Thr157= (c.471G>A) pathogenic?

ROR2 p.Thr157= (c.471G>A) is classified Benign/Likely benign in ROR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Low-frequency (popmax 2.59%, afr); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Thr157= (c.471G>A)?

ROR2 p.Thr157= (c.471G>A) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Thr157= (c.471G>A) in the general population?

ROR2 p.Thr157= (c.471G>A) is low-frequency (popmax 2.59%, afr) (gnomAD).

ROR2 p.Thr157=

c.471G>A · rs78781083 · VCV367516

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.59%, afr)

Conditions

autosomal recessive Robinow syndrome

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 -4.5	GERP -5.1
Overall
CADD	7.401	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.59% African / African-American · 1,940/74,994 alleles

Filtering AF 2.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.45%

Overall 0.138% 2,233/1,613,806 alleles · low-frequency exomes 1,085/1,461,546 · genomes 1,148/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.59%	39
Admixed American	0.22%	455
Remaining individualsnot grpmax-eligible	0.176%	568
Middle Eastern	0.0825%	1,212
South Asian	0.00769%	13,012
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.00314%	31,885
East Asian	0.00223%	44,872

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.Thr157=
Coding: c.471G>A
MANE Select: NM_004560
dbSNP: rs78781083
Type: single nucleotide variant
Location: chr9:91756094 (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

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-thr157 (accessed [today's date]).

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