Is CNGA1 p.Ser563fs (c.1689_1702del) pathogenic?

CNGA1 p.Ser563fs (c.16891702del) is classified Likely pathogenic in CNGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). Very rare (popmax 0.00134%, afr); Associated with retinitis pigmentosa 49.

What condition is associated with CNGA1 p.Ser563fs (c.1689_1702del)?

CNGA1 p.Ser563fs (c.1689_1702del) is associated with retinitis pigmentosa 49 (ClinVar).

How common is CNGA1 p.Ser563fs (c.1689_1702del) in the general population?

CNGA1 p.Ser563fs (c.1689_1702del) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CNGA1 p.Ser563fs

c.1689_1702del · VCV3590578

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

retinitis pigmentosa 49

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8	GERP 4.3, phastCons 1
Overall
CADD	35.0	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 0.00134% African / African-American · 1/74,906 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,906
European (non-Finnish)	0.000508%	196,673

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: CNGA1
Protein: p.Ser563fs
Coding: c.1689_1702del
MANE Select: NM_001379270
Type: Deletion
Location: chr4:47936780 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB
Residue 563: the 'cyclic nucleotide-binding domain' region; a β-strand

Full CNGA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 49 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CNGA1 p.Asn175_Trp176insTer Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Asp575fs Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Gly60fs Pathogenic ★★ same condition
CNGA1 p.Leu85fs Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Thr177fs Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Thr443fs Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Thr582fs Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Gln74fs 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/cnga1-p-ser563fs (accessed [today's date]).

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