Is CEP290 p.Ala560= (c.1680T>C) pathogenic?

CEP290 p.Ala560= (c.1680T>C) is classified Likely benign in CEP290 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-25). Very rare (popmax 0.00052%, nfe); Associated with Meckel syndrome.

What condition is associated with CEP290 p.Ala560= (c.1680T>C)?

CEP290 p.Ala560= (c.1680T>C) is associated with Meckel syndrome, Joubert syndrome, nephronophthisis (ClinVar).

How common is CEP290 p.Ala560= (c.1680T>C) in the general population?

CEP290 p.Ala560= (c.1680T>C) is very rare (popmax 0.00052%, nfe) (gnomAD).

CEP290 p.Ala560=

c.1680T>C · rs777669368 · VCV512061

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00052%, nfe)

Conditions

Meckel 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 5	GERP -0.099, phastCons 1
Overall
CADD	11.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00052% European (non-Finnish) · 6/1,154,510 alleles

Filtering AF 0.000187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000123%

Overall 0.000383% 6/1,567,704 alleles · very rare

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.Ala560=
Coding: c.1680T>C
MANE Select: NM_025114
dbSNP: rs777669368
Type: single nucleotide variant
Location: chr12:88118514 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 560: 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 p.Ala560Val 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-ala560 (accessed [today's date]).

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