Is ROR2 p.Val629Met (c.1885G>A) pathogenic?

ROR2 p.Val629Met (c.1885G>A) is classified Uncertain significance in ROR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-21). AlphaMissense: likely benign (0.2541); Ultra-rare (popmax 0.075%, amr); Associated with Inborn genetic diseases.

What condition is associated with ROR2 p.Val629Met (c.1885G>A)?

ROR2 p.Val629Met (c.1885G>A) is associated with Inborn genetic diseases, brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Val629Met (c.1885G>A) in the general population?

ROR2 p.Val629Met (c.1885G>A) is ultra-rare (popmax 0.075%, amr) (gnomAD).

What do computational predictors say about ROR2 p.Val629Met (c.1885G>A)?

AlphaMissense predicts likely benign (score 0.2541) — an in-silico prediction, not a clinical call.

ROR2 p.Val629Met

c.1885G>A · rs148844963 · VCV286284

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2541 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.075%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2541	likely benign
REVEL	0.637	indeterminate
SaProt	LLR -12.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	26.2	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 0.075% Admixed American · 45/60,014 alleles

Filtering AF 0.0575% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.00465% 75/1,614,102 alleles · ultra-rare exomes 59/1,461,880 · genomes 16/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.075%	1,334
East Asian	0.0134%	7,482
African / African-American	0.0107%	9,367
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Finnishnot grpmax-eligible	0.00156%	64,038
South Asian	0.0011%	91,094
European (non-Finnish)	0.000932%	107,277

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.Val629Met
Coding: c.1885G>A
MANE Select: NM_004560
dbSNP: rs148844963
Type: single nucleotide variant
Location: chr9:91724609 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 629: the protein kinase domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachydactyly type B1 autosomal recessive Robinow syndrome

Similar variants

ROR2 p.Val629= Likely benign ★ 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-val629met (accessed [today's date]).

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