Is CEP290 p.Glu1981= (c.5943G>A) pathogenic?

CEP290 p.Glu1981= (c.5943G>A) is classified Likely benign in CEP290 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). Very rare (popmax 0.00167%, amr); Associated with Joubert syndrome.

What condition is associated with CEP290 p.Glu1981= (c.5943G>A)?

CEP290 p.Glu1981= (c.5943G>A) is associated with Joubert syndrome, Meckel syndrome, nephronophthisis (ClinVar).

How common is CEP290 p.Glu1981= (c.5943G>A) in the general population?

CEP290 p.Glu1981= (c.5943G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

CEP290 p.Glu1981=

c.5943G>A · rs1396645704 · VCV2419885

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 0.075	GERP 0.65, phastCons 0.84
Overall
CADD	5.452	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,822 alleles

Overall 0.000137% 2/1,458,274 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,822
Remaining individualsnot grpmax-eligible	0.0016%	62,358

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.Glu1981=
Coding: c.5943G>A
MANE Select: NM_025114
dbSNP: rs1396645704
Type: single nucleotide variant
Location: chr12:88071362 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 1981: a UniProt-annotated variant site (in lca10; also found in a patient with night blindness and hearing loss); a UniProt-annotated variant site (in lca10); a UniProt-annotated variant site (in lca10, slsn6 and mks4); a UniProt-annotated variant site (in lca10 and slsn6); a UniProt-annotated variant site (in mks4 and jbts5); the 'self-association (with itself or n-terminus)' region

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.Glu1981Ter Pathogenic/Likely pathogenic ★★ same residue
CEP290 p.Glu1981fs Pathogenic ★ 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-glu1981 (accessed [today's date]).

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