Is ROR2 p.Asp935Glu (c.2805C>G) pathogenic?

ROR2 p.Asp935Glu (c.2805C>G) is classified Conflicting classifications of pathogenicity in ROR2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0752); Low-frequency (popmax 1.01%, nfe); Associated with autosomal recessive Robinow syndrome.

What condition is associated with ROR2 p.Asp935Glu (c.2805C>G)?

ROR2 p.Asp935Glu (c.2805C>G) is associated with autosomal recessive Robinow syndrome, brachydactyly type B1 (ClinVar).

How common is ROR2 p.Asp935Glu (c.2805C>G) in the general population?

ROR2 p.Asp935Glu (c.2805C>G) is low-frequency (popmax 1.01%, nfe) (gnomAD).

What do computational predictors say about ROR2 p.Asp935Glu (c.2805C>G)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

ROR2 p.Asp935Glu

c.2805C>G · rs41277835 · VCV159819

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.01%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive Robinow syndrome

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -3.1
Regional constraint	o/e 0.93	unconstrained · MANE · 226 kb · p 0.007 · regional, not allelic
Overall
CADD	0.109	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 1.01% European (non-Finnish) · 11,870/1,179,962 alleles

Filtering AF 0.991% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.985%

Overall 0.803% 12,959/1,613,804 alleles · low-frequency exomes 12,256/1,461,492 · genomes 703/152,312 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.01%	99
South Asian	0.489%	205
Remaining individualsnot grpmax-eligible	0.461%	217
Finnishnot grpmax-eligible	0.293%	341
African / African-American	0.133%	750
Admixed American	0.0866%	1,154
Middle Eastern	0.0496%	2,017
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
East Asian	0.00223%	44,882

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.Asp935Glu
Coding: c.2805C>G
MANE Select: NM_004560
dbSNP: rs41277835
Type: single nucleotide variant
Location: chr9:91723689 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 935: a UniProt-annotated variant site (in)

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-asp935glu (accessed [today's date]).

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