Is CEP290 p.Ala697= (c.2091G>A) pathogenic?

CEP290 p.Ala697= (c.2091G>A) is classified Likely benign in CEP290 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-24). Ultra-rare (popmax 0.0159%, eas); Associated with inherited retinal dystrophy.

What condition is associated with CEP290 p.Ala697= (c.2091G>A)?

CEP290 p.Ala697= (c.2091G>A) is associated with inherited retinal dystrophy, Joubert syndrome, Meckel syndrome (ClinVar).

How common is CEP290 p.Ala697= (c.2091G>A) in the general population?

CEP290 p.Ala697= (c.2091G>A) is ultra-rare (popmax 0.0159%, eas) (gnomAD).

CEP290 p.Ala697=

c.2091G>A · rs1399023990 · VCV1145851

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, eas)

Conditions

inherited retinal dystrophy

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 -0.095	GERP -5.2, phastCons 0.096
Overall
CADD	8.592	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0159% East Asian · 7/43,968 alleles

Filtering AF 0.00739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00523%

Overall 0.00125% 20/1,602,482 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0159%	6,281
European (non-Finnish)	0.00111%	90,383

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.Ala697=
Coding: c.2091G>A
MANE Select: NM_025114
dbSNP: rs1399023990
Type: single nucleotide variant
Location: chr12:88111820 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 697: a UniProt-annotated variant site (in lca10; also found in a patient with night blindness and hearing loss); the 'interaction with iqcb1' region

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome Meckel syndrome nephronophthisis

Similar variants

CEP290 p.Ala697Val Uncertain significance ★★ ⚠ same residue
CEP290 p.Ala697Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
CEP290 p.Ala697Pro 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

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-ala697 (accessed [today's date]).

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