Is CEP290 p.Arg360= (c.1078C>A) pathogenic?

CEP290 p.Arg360= (c.1078C>A) is classified Likely benign in CEP290 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-04-12). Very rare (popmax 9.98e-05%, nfe); Associated with Joubert syndrome.

What condition is associated with CEP290 p.Arg360= (c.1078C>A)?

CEP290 p.Arg360= (c.1078C>A) is associated with Joubert syndrome, Meckel syndrome, nephronophthisis (ClinVar).

How common is CEP290 p.Arg360= (c.1078C>A) in the general population?

CEP290 p.Arg360= (c.1078C>A) is very rare (popmax 9.98e-05%, nfe) (gnomAD).

CEP290 p.Arg360=

c.1078C>A · rs776645403 · VCV1087751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 9.98e-05%, nfe)

Conditions

Joubert 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 4.1	GERP 1.6, phastCons 1
Overall
CADD	9.613	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.98e-05% European (non-Finnish) · 1/1,002,050 alleles

Overall 7.65e-05% 1/1,307,844 alleles · very rare exomes 1/1,156,288 · genomes 0/151,556 · joint denominator

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: CEP290
Protein: p.Arg360=
Coding: c.1078C>A
MANE Select: NM_025114
dbSNP: rs776645403
Type: single nucleotide variant
Location: chr12:88125357 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 360: the 'self-association (with itself or c-terminus)' region; a UniProt-annotated variant site (in lca10; also found in a patient with night blindness and hearing loss)

Full CEP290 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: Meckel syndrome nephronophthisis

Similar variants

CEP290 p.Arg360Ter Pathogenic ★★ same residue
CEP290 p.Arg360Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CEP290 c.1189+1G>A Pathogenic ★★★ same condition
CEP290 c.1189+2T>C Pathogenic ★★★ same condition
CEP290 c.297+1G>T Pathogenic ★★★ same condition
CEP290 c.2991+1655A>G Pathogenic ★★★ same condition
CEP290 c.6271-8T>G Pathogenic ★★★ same condition
CEP290 p.Arg1272Ter 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/cep290-p-arg360 (accessed [today's date]).

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