Is CEP290 p.Arg151Ter (c.451C>T) pathogenic?

CEP290 p.Arg151Ter (c.451C>T) is classified Pathogenic/Likely pathogenic in CEP290 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-12). Very rare (popmax 0.00372%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP290 p.Arg151Ter (c.451C>T)?

CEP290 p.Arg151Ter (c.451C>T) is associated with Inborn genetic diseases, retinal disorder, Joubert syndrome 5 (ClinVar).

How common is CEP290 p.Arg151Ter (c.451C>T) in the general population?

CEP290 p.Arg151Ter (c.451C>T) is very rare (popmax 0.00372%, nfe) (gnomAD).

CEP290 p.Arg151Ter

c.451C>T · rs757641323 · VCV372761

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00372%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 54
Splicing
SpliceAI	Δ0.33	acceptor loss · deltas
Pangolin	Δ0.54	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 2.1, phastCons 1
Overall
CADD	42.0	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 0.00372% European (non-Finnish) · 42/1,127,876 alleles

Filtering AF 0.00279% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00247%

Overall 0.00295% 44/1,493,020 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00372%	26,854
East Asian	0.00261%	38,382
Remaining individualsnot grpmax-eligible	0.00174%	57,510

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.Arg151Ter
Coding: c.451C>T
MANE Select: NM_025114
dbSNP: rs757641323
Type: single nucleotide variant
Location: chr12:88131209 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 151: 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); the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

CEP290 p.Arg151Gln Uncertain significance ★★ ⚠ same residue
CEP290 p.Arg151Pro 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

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-arg151ter (accessed [today's date]).

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