Is ROR2 p.Asp672Asn (c.2014G>A) pathogenic?

ROR2 p.Asp672Asn (c.2014G>A) is classified Uncertain significance in ROR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-14). AlphaMissense: ambiguous (0.4575); Ultra-rare (popmax 0.0122%, nfe); Associated with intellectual disability.

What condition is associated with ROR2 p.Asp672Asn (c.2014G>A)?

ROR2 p.Asp672Asn (c.2014G>A) is associated with intellectual disability, brachydactyly type B1, autosomal recessive Robinow syndrome (ClinVar).

How common is ROR2 p.Asp672Asn (c.2014G>A) in the general population?

ROR2 p.Asp672Asn (c.2014G>A) is ultra-rare (popmax 0.0122%, nfe) (gnomAD).

What do computational predictors say about ROR2 p.Asp672Asn (c.2014G>A)?

AlphaMissense predicts ambiguous (score 0.4575) — an in-silico prediction, not a clinical call.

ROR2 p.Asp672Asn

c.2014G>A · rs55651110 · VCV1012281

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4575 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, nfe)

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.4575	ambiguous
REVEL	0.401	indeterminate
SaProt	LLR -12.00	damaging
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	26.9	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 0.0122% European (non-Finnish) · 144/1,180,036 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00994%

Overall 0.0108% 175/1,614,054 alleles · ultra-rare exomes 164/1,461,866 · genomes 11/152,188 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,691
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)grpmax	0.0122%	8,195
South Asian	0.00549%	18,217
African / African-American	0.004%	24,980
Admixed American	0.00167%	60,010

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp672Asn
Coding: c.2014G>A
MANE Select: NM_004560
dbSNP: rs55651110
Type: single nucleotide variant
Location: chr9:91724480 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.35 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 6 PDB
Residue 672: a UniProt-annotated variant site (in); the protein kinase domain; an α-helix

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachydactyly type B1 autosomal recessive Robinow syndrome

Similar variants

ROR2 p.Asp672Tyr 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-asp672asn (accessed [today's date]).

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