Is C1R p.Cys89Arg (c.265T>C) pathogenic?

C1R p.Cys89Arg (c.265T>C) is classified Likely pathogenic in C1R (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-25). AlphaMissense: likely pathogenic (0.9755); Absent from gnomAD v4.1; Associated with Ehlers-Danlos syndrome.

What condition is associated with C1R p.Cys89Arg (c.265T>C)?

C1R p.Cys89Arg (c.265T>C) is associated with Ehlers-Danlos syndrome (ClinVar).

How common is C1R p.Cys89Arg (c.265T>C) in the general population?

C1R p.Cys89Arg (c.265T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C1R p.Cys89Arg (c.265T>C)?

AlphaMissense predicts likely pathogenic (score 0.9755) — an in-silico prediction, not a clinical call.

C1R p.Cys89Arg

c.265T>C · rs1938242419 · VCV972707

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ehlers-Danlos syndrome

Computational evidence

Protein change
AlphaMissense	0.9755	likely pathogenic ✓ concordant with ClinVar · top 6% in C1R
REVEL	0.72	pathogenic-leaning
SaProt	LLR -16.31	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 10 kb · p 1.4e-08 · regional, not allelic
Overall
CADD	24.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C1R
Protein: p.Cys89Arg
Coding: c.265T>C
MANE Select: NM_001733
dbSNP: rs1938242419
Type: single nucleotide variant
Location: chr12:7090215 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 87.33 · 12 PDB
Residue 89: a disulfide bond; the cub 1 domain

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

Disease context

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

Similar variants

C1R p.Cys89= Likely benign ★ same residue
C1R p.Arg301Pro Pathogenic ★★ ⚠ same type
C1R p.Asp290Gly Pathogenic/Likely pathogenic ★★ same type
C1R p.Cys338Arg Pathogenic ★★ same type
C1R p.Cys371Trp Pathogenic ★★ same type
C1R p.Gly297Asp Pathogenic/Likely pathogenic ★★ same type
C1R p.His642Gln Uncertain significance ★★ ⚠ same type
C1R p.Leu285Met Uncertain significance ★★ ⚠ same type

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-cys89arg (accessed [today's date]).

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