Is CEP290 p.Arg2011Ter (c.6031C>T) pathogenic?

CEP290 p.Arg2011Ter (c.6031C>T) is classified Pathogenic in CEP290 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-05-21). Very rare (popmax 0.00229%, eas); Associated with Meckel syndrome.

What condition is associated with CEP290 p.Arg2011Ter (c.6031C>T)?

CEP290 p.Arg2011Ter (c.6031C>T) is associated with Meckel syndrome, Joubert syndrome 5, Senior-Loken syndrome 6 (ClinVar).

How common is CEP290 p.Arg2011Ter (c.6031C>T) in the general population?

CEP290 p.Arg2011Ter (c.6031C>T) is very rare (popmax 0.00229%, eas) (gnomAD).

CEP290 p.Arg2011Ter

c.6031C>T · rs750073051 · VCV871059

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00229%, eas)

Conditions

Meckel syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 44 of 54
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.4	GERP 1.3, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% East Asian · 1/43,740 alleles

Filtering AF 0.000883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000722%

Overall 0.00119% 19/1,593,038 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00229%	43,740
Remaining individualsnot grpmax-eligible	0.00162%	61,628
European (non-Finnish)	0.00145%	69,012

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.Arg2011Ter
Coding: c.6031C>T
MANE Select: NM_025114
dbSNP: rs750073051
Type: single nucleotide variant
Location: chr12:88068626 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 2011: 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

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

Also linked: Joubert syndrome 5 Senior-Loken syndrome 6 Meckel syndrome, type 4 Leber congenital amaurosis 10 Bardet-Biedl syndrome 14 Joubert syndrome Leber congenital amaurosis nephronophthisis

Similar variants

CEP290 p.Arg2011Gln Uncertain significance ★ ⚠ 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
CEP290 p.Arg1465Ter 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-arg2011ter (accessed [today's date]).

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