Is CNGA3 p.Arg603Pro (c.1808G>C) pathogenic?

CNGA3 p.Arg603Pro (c.1808G>C) is classified Likely pathogenic in CNGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely pathogenic (0.9813); Absent from gnomAD v4.1.

How common is CNGA3 p.Arg603Pro (c.1808G>C) in the general population?

CNGA3 p.Arg603Pro (c.1808G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNGA3 p.Arg603Pro (c.1808G>C)?

AlphaMissense predicts likely pathogenic (score 0.9813) — an in-silico prediction, not a clinical call.

CNGA3 p.Arg603Pro

c.1808G>C · rs372215423 · VCV1024475

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9813 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9813	likely pathogenic ✓ concordant with ClinVar · top 5% in CNGA3
REVEL	0.771	pathogenic-leaning
SaProt	LLR -15.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.87, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,336 bp · p 0.34 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: CNGA3
Protein: p.Arg603Pro
Coding: c.1808G>C
MANE Select: NM_001298
dbSNP: rs372215423
Type: single nucleotide variant
Location: chr2:98396978 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 603: an α-helix; the 'cyclic nucleotide-binding domain' region

Full CNGA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNGA3 p.Arg603Trp Uncertain significance ★★ ⚠ same residue
CNGA3 p.Arg603Gln Uncertain significance ★ same residue
CNGA3 c.216-1G>A Likely pathogenic ★★ same type
CNGA3 c.396-11C>G Pathogenic/Likely pathogenic ★★ same type
CNGA3 c.450-1G>A Pathogenic ★★ same type
CNGA3 p.Ala262Pro Likely pathogenic ★★ ⚠ same type
CNGA3 p.Ala318Thr Pathogenic ★★ same type
CNGA3 p.Ala469Thr Pathogenic/Likely pathogenic ★★ ⚠ same type

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/cnga3-p-arg603pro (accessed [today's date]).

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