Is ROR2 p.Glu170Lys (c.508G>A) pathogenic?

ROR2 p.Glu170Lys (c.508G>A) is classified Uncertain significance in ROR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely benign (0.167); Very rare (popmax 0.00267%, afr); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Glu170Lys (c.508G>A)?

ROR2 p.Glu170Lys (c.508G>A) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Glu170Lys (c.508G>A) in the general population?

ROR2 p.Glu170Lys (c.508G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ROR2 p.Glu170Lys (c.508G>A)?

AlphaMissense predicts likely benign (score 0.167) — an in-silico prediction, not a clinical call.

ROR2 p.Glu170Lys

c.508G>A · VCV3597783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive Robinow syndrome

Computational evidence

Protein change
AlphaMissense	0.167	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -7.05	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 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,614,066 alleles · very rare exomes 5/1,461,882 · genomes 2/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
South Asian	0.0022%	45,542
European (non-Finnish)	0.000254%	393,348

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.Glu170Lys
Coding: c.508G>A
MANE Select: NM_004560
Type: single nucleotide variant
Location: chr9:91737505 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 170: the fz domain

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-glu170lys (accessed [today's date]).

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