Is DDR2 p.Ile751= (c.2253C>T) pathogenic?

DDR2 p.Ile751= (c.2253C>T) is classified Conflicting classifications of pathogenicity in DDR2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-02). Rare (popmax 0.154%, eas); Associated with spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome.

How common is DDR2 p.Ile751= (c.2253C>T) in the general population?

DDR2 p.Ile751= (c.2253C>T) is rare (popmax 0.154%, eas) (gnomAD).

DDR2 p.Ile751=

Q: What condition is associated with DDR2 p.Ile751= (c.2253C>T)?

DDR2 p.Ile751= (c.2253C>T) is associated with spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (ClinVar).

Q: How is Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2253C>T · rs768825317 · VCV293382

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.154%, eas)

Conditions

spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP 1.1, phastCons 0.99
Overall
CADD	8.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.154% East Asian · 69/44,870 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00465% 75/1,614,058 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.154%	650
Remaining individualsnot grpmax-eligible	0.0064%	15,625
Admixed American	0.00167%	60,006
European (non-Finnish)	8.47e-05%	1,179,958

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: DDR2
Protein: p.Ile751=
Coding: c.2253C>T
MANE Select: NM_006182
dbSNP: rs768825317
Type: single nucleotide variant
Location: chr1:162776340 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.57 · 5 PDB
Residue 751: the protein kinase domain; a turn

Full DDR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DDR2 p.Arg752Cys Likely pathogenic ★★ same condition
DDR2 c.-27-11G>C Uncertain significance ★★ same condition
DDR2 c.*48A>G Uncertain significance ★★ same condition
DDR2 p.Arg128His Uncertain significance ★★ ⚠ same condition
DDR2 p.Arg165Gln Uncertain significance ★★ ⚠ same condition
DDR2 p.Arg260Trp Uncertain significance ★★ ⚠ same condition
DDR2 p.Arg307Cys Uncertain significance ★★ ⚠ same condition
DDR2 p.Arg668His 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/ddr2-p-ile751 (accessed [today's date]).

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