Is DDR2 p.Arg752Ser (c.2254C>A) pathogenic?

DDR2 p.Arg752Ser (c.2254C>A) is classified Uncertain significance in DDR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely pathogenic (0.9996); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DDR2 p.Arg752Ser (c.2254C>A)?

DDR2 p.Arg752Ser (c.2254C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DDR2 p.Arg752Ser (c.2254C>A) in the general population?

DDR2 p.Arg752Ser (c.2254C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DDR2 p.Arg752Ser (c.2254C>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

DDR2 p.Arg752Ser

c.2254C>A · VCV3500333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 1% in DDR2
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -16.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 8,206 bp · p 2.1e-15 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,179,962 alleles

Overall 6.84e-05% 1/1,461,774 alleles · very rare

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.Arg752Ser
Coding: c.2254C>A
MANE Select: NM_006182
Type: single nucleotide variant
Location: chr1:162776341 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.57 · 5 PDB
Residue 752: a UniProt-annotated variant site (in semd-sl; causes retention in an intracellular compartment and thereby abolishes signaling in response collagen binding); the protein kinase domain; a turn

Full DDR2 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

Similar variants

DDR2 p.Arg752Cys Likely pathogenic ★★ same residue
DDR2 p.Arg752His Uncertain significance ★★ ⚠ same residue
DDR2 p.Arg399Gln Uncertain significance ★★ ⚠ same condition
DDR2 p.Arg742Gln Uncertain significance ★★ ⚠ same condition
DDR2 p.Arg742Trp Uncertain significance ★★ ⚠ same condition
DDR2 p.Asn686Ser Uncertain significance ★★ ⚠ same condition
DDR2 p.Asn721Ser Uncertain significance ★★ ⚠ same condition
DDR2 p.Ile278Val 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-arg752ser (accessed [today's date]).

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