Is CNGA3 p.Pro592= (c.1776C>T) pathogenic?

CNGA3 p.Pro592= (c.1776C>T) is classified Likely benign in CNGA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-01). Ultra-rare (popmax 0.066%, mid).

How common is CNGA3 p.Pro592= (c.1776C>T) in the general population?

CNGA3 p.Pro592= (c.1776C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

CNGA3 p.Pro592=

c.1776C>T · rs201637471 · VCV777997

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

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 -13	GERP -3.7
Overall
CADD	0.285	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0262% 423/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0875%	1,142
Middle Easterngrpmax	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0448%	2,232
African / African-American	0.0373%	2,680
European (non-Finnish)	0.0258%	3,869
East Asian	0.00446%	22,442

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CNGA3
Protein: p.Pro592=
Coding: c.1776C>T
MANE Select: NM_001298
dbSNP: rs201637471
Type: single nucleotide variant
Location: chr2:98396946 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 592: 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.Pro592Leu Pathogenic/Likely pathogenic ★★ same residue
CNGA3 p.Pro592Ala Conflicting classifications of pathogenicity ★ ⚠ 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-pro592 (accessed [today's date]).

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