Is C1R p.Val50Asp (c.149_150delinsAT) pathogenic?

C1R p.Val50Asp (c.149150delinsAT) is classified Pathogenic in C1R (ClinVar, Single submitter, 3 submitters; last evaluated 2016-08-23). Absent from gnomAD; Associated with Ehlers-Danlos syndrome, periodontal type 1.

What condition is associated with C1R p.Val50Asp (c.149_150delinsAT)?

C1R p.Val50Asp (c.149_150delinsAT) is associated with Ehlers-Danlos syndrome, periodontal type 1, Ehlers-Danlos syndrome, periodontal type 2 (ClinVar).

How common is C1R p.Val50Asp (c.149_150delinsAT) in the general population?

C1R p.Val50Asp (c.149_150delinsAT) is absent from gnomAD (gnomAD).

How is Periodontal Ehlers-Danlos syndrome inherited?

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

C1R p.Val50Asp

c.149_150delinsAT · rs1057519025 · VCV372130

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Ehlers-Danlos syndrome, periodontal type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.45	GERP -1.8, phastCons 0.007
Regional constraint	o/e 1.39	unconstrained · MANE · 10 kb · p 1.4e-08 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C1R
Protein: p.Val50Asp
Coding: c.149_150delinsAT
MANE Select: NM_001733
dbSNP: rs1057519025
Type: Indel
Location: chr12:7091533 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 87.33 · 12 PDB
Residue 50: the cub 1 domain; a UniProt-annotated variant site (in edspd1; the mutant is not secreted but retained intracellularly; requires 2 nucleotide substitutions)

Full C1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome, periodontal type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, periodontal type 2

For Periodontal Ehlers-Danlos syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

C1R p.Arg401_Tyr405delinsHisValIle Pathogenic ★ same condition
C1R p.Ile306_Cys309delinsArgThr Pathogenic ★ same condition
C1R p.Val50= Likely benign ★ same residue
C1R p.Arg301Pro Pathogenic ★★ ⚠ same condition
C1R p.Asp290Gly Pathogenic/Likely pathogenic ★★ same condition
C1R p.Cys338Arg Pathogenic ★★ same condition
C1R p.Cys371Trp Pathogenic ★★ same condition
C1R p.Gly297Asp Pathogenic/Likely pathogenic ★★ 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/c1r-p-val50asp (accessed [today's date]).

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