Is ROR2 p.Val909= (c.2727G>A) pathogenic?

ROR2 p.Val909= (c.2727G>A) is classified Benign in ROR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-22). Low-frequency (popmax 4.2%, afr); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Val909= (c.2727G>A)?

ROR2 p.Val909= (c.2727G>A) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Val909= (c.2727G>A) in the general population?

ROR2 p.Val909= (c.2727G>A) is low-frequency (popmax 4.2%, afr) (gnomAD).

ROR2 p.Val909=

c.2727G>A · rs56091954 · VCV287691

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.2%, 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 0.36	GERP -0.52, phastCons 0.99
Overall
CADD	0.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.2% African / African-American · 3,152/75,026 alleles

Filtering AF 4.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.03%

Overall 0.219% 3,542/1,613,806 alleles · low-frequency exomes 1,765/1,461,506 · genomes 1,777/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.2%	24
Admixed American	0.295%	339
Remaining individualsnot grpmax-eligible	0.262%	381
Middle Eastern	0.066%	1,516
South Asian	0.00878%	11,386
European (non-Finnish)	0.00314%	31,893

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.Val909=
Coding: c.2727G>A
MANE Select: NM_004560
dbSNP: rs56091954
Type: single nucleotide variant
Location: chr9:91723767 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 909: the 'disordered' region

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 p.Val909Met Uncertain significance ★★ ⚠ same residue
ROR2 p.Val909Leu 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

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-val909 (accessed [today's date]).

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