Is CNGA1 p.Ala559Pro (c.1675G>C) pathogenic?

CNGA1 p.Ala559Pro (c.1675G>C) is classified Likely pathogenic in CNGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with retinitis pigmentosa 49.

What condition is associated with CNGA1 p.Ala559Pro (c.1675G>C)?

CNGA1 p.Ala559Pro (c.1675G>C) is associated with retinitis pigmentosa 49 (ClinVar).

How common is CNGA1 p.Ala559Pro (c.1675G>C) in the general population?

CNGA1 p.Ala559Pro (c.1675G>C) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about CNGA1 p.Ala559Pro (c.1675G>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

CNGA1 p.Ala559Pro

c.1675G>C · VCV4755504

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

retinitis pigmentosa 49

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar · top 2% in CNGA1
REVEL	0.968	strongly pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A563P vs ClinVar A559P) — verify the residue.

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: CNGA1
Protein: p.Ala559Pro
Coding: c.1675G>C
MANE Select: NM_001379270
Type: single nucleotide variant
Location: chr4:47936807 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB

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 c.107+2T>G Likely pathogenic ★★ same condition
CNGA1 c.545+2T>A Likely pathogenic ★★ same condition
CNGA1 c.546-1G>C Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Arg214Ter Pathogenic ★★ same condition
CNGA1 p.Arg28Ter Pathogenic ★★ same condition
CNGA1 p.Arg420Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Arg510Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Arg625Ter Pathogenic/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/cnga1-p-ala559pro (accessed [today's date]).

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