Is CNGA3 p.Arg75= (c.225C>T) pathogenic?

CNGA3 p.Arg75= (c.225C>T) is classified Conflicting classifications of pathogenicity in CNGA3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-08-31). Rare (popmax 0.308%, eas); Associated with achromatopsia 2.

What condition is associated with CNGA3 p.Arg75= (c.225C>T)?

CNGA3 p.Arg75= (c.225C>T) is associated with achromatopsia 2 (ClinVar).

How common is CNGA3 p.Arg75= (c.225C>T) in the general population?

CNGA3 p.Arg75= (c.225C>T) is rare (popmax 0.308%, eas) (gnomAD).

How is Achromatopsia inherited?

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

CNGA3 p.Arg75=

c.225C>T · rs200404774 · VCV337654

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.308%, eas)

Conditions

achromatopsia 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.9	GERP -3.4
Overall
CADD	5.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.308% East Asian · 138/44,876 alleles

Filtering AF 0.266% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.25%

Overall 0.00886% 143/1,614,176 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.308%	325
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.000254%	393,348

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.Arg75=
Coding: c.225C>T
MANE Select: NM_001298
dbSNP: rs200404774
Type: single nucleotide variant
Location: chr2:98380184 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB

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

Disease context

achromatopsia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Achromatopsia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

CNGA3 p.Arg75Cys Uncertain significance ★★ ⚠ same residue
CNGA3 p.Arg75His Likely benign ★ same residue
CNGA3 c.216-1G>A Likely pathogenic ★★ same condition
CNGA3 c.396-11C>G Pathogenic/Likely pathogenic ★★ same condition
CNGA3 c.450-1G>A Pathogenic ★★ same condition
CNGA3 p.Ala262Pro Likely pathogenic ★★ ⚠ same condition
CNGA3 p.Arg221Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA3 p.Arg223Gly 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/cnga3-p-arg75 (accessed [today's date]).

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