Is CEP290 p.Phe496= (c.1488C>T) pathogenic?

CEP290 p.Phe496= (c.1488C>T) is classified Likely benign in CEP290 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). No allele count reported in gnomAD v4.1 (AN 1,543,738); Associated with Meckel syndrome.

What condition is associated with CEP290 p.Phe496= (c.1488C>T)?

CEP290 p.Phe496= (c.1488C>T) is associated with Meckel syndrome, Joubert syndrome, nephronophthisis (ClinVar).

How common is CEP290 p.Phe496= (c.1488C>T) in the general population?

CEP290 p.Phe496= (c.1488C>T) is no allele count reported in gnomAD v4.1 (AN 1,543,738) (gnomAD).

CEP290 p.Phe496=

c.1488C>T · VCV4787251

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,543,738)

Conditions

Meckel syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.73	GERP -1.4, phastCons 1
Overall
CADD	6.783	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,543,738). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CEP290
Protein: p.Phe496=
Coding: c.1488C>T
MANE Select: NM_025114
Type: single nucleotide variant
Location: chr12:88120148 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 496: 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

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

Also linked: Joubert syndrome nephronophthisis

Similar variants

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
CEP290 p.Arg1752Trp Likely 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-phe496 (accessed [today's date]).

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