Is CEP290 p.Arg151Pro (c.452G>C) pathogenic?

CEP290 p.Arg151Pro (c.452G>C) is classified Uncertain significance in CEP290 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: likely pathogenic (0.9803); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CEP290 p.Arg151Pro (c.452G>C)?

CEP290 p.Arg151Pro (c.452G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP290 p.Arg151Pro (c.452G>C) in the general population?

CEP290 p.Arg151Pro (c.452G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP290 p.Arg151Pro (c.452G>C)?

AlphaMissense predicts likely pathogenic (score 0.9803) — an in-silico prediction, not a clinical call.

CEP290 p.Arg151Pro

c.452G>C · VCV3831824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9803 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9803	likely pathogenic · top 1% in CEP290
REVEL	0.338	indeterminate
SaProt	LLR -11.52	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 92 kb · p 0.89 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CEP290
Protein: p.Arg151Pro
Coding: c.452G>C
MANE Select: NM_025114
Type: single nucleotide variant
Location: chr12:88131208 (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

Similar variants

CEP290 p.Arg151Ter Pathogenic/Likely pathogenic ★★ same residue
CEP290 p.Arg151Gln Uncertain significance ★★ ⚠ same residue
CEP290 c.2587-3C>T Uncertain significance ★★ same condition
CEP290 c.5226+6T>G Uncertain significance ★★ same condition
CEP290 p.Ala1215Thr Uncertain significance ★★ ⚠ same condition
CEP290 p.Ala1277Val Uncertain significance ★★ ⚠ same condition
CEP290 p.Ala1566Val Uncertain significance ★★ ⚠ same condition
CEP290 p.Ala1743Val Uncertain significance ★★ ⚠ 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-arg151pro (accessed [today's date]).

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