Is ROR2 p.His571Arg (c.1712A>G) pathogenic?

ROR2 p.His571Arg (c.1712A>G) is classified Benign/Likely benign in ROR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1926); Rare (popmax 0.954%, sas); Associated with brachydactyly type B1.

What condition is associated with ROR2 p.His571Arg (c.1712A>G)?

ROR2 p.His571Arg (c.1712A>G) is associated with brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.His571Arg (c.1712A>G) in the general population?

ROR2 p.His571Arg (c.1712A>G) is rare (popmax 0.954%, sas) (gnomAD).

What do computational predictors say about ROR2 p.His571Arg (c.1712A>G)?

AlphaMissense predicts likely benign (score 0.1926) — an in-silico prediction, not a clinical call.

ROR2 p.His571Arg

c.1712A>G · rs376970201 · VCV289424

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1926 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.954%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

brachydactyly type B1

Computational evidence

Protein change
AlphaMissense	0.1926	likely benign
REVEL	0.478	indeterminate
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.954% South Asian · 868/91,020 alleles

Filtering AF 0.901% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.88%

Overall 0.0594% 957/1,611,948 alleles · rare exomes 906/1,459,770 · genomes 51/152,178 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.954%	105
Remaining individualsnot grpmax-eligible	0.0449%	2,230
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.00475%	21,043
African / African-American	0.004%	24,996
East Asian	0.00223%	44,808

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.His571Arg
Coding: c.1712A>G
MANE Select: NM_004560
dbSNP: rs376970201
Type: single nucleotide variant
Location: chr9:91724782 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 571: the protein kinase 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 p.His571Tyr 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-his571arg (accessed [today's date]).

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