Is CNGA3 p.Pro48= (c.144G>A) pathogenic?

CNGA3 p.Pro48= (c.144G>A) is classified Conflicting classifications of pathogenicity in CNGA3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0897%, mid); Associated with achromatopsia 2.

What condition is associated with CNGA3 p.Pro48= (c.144G>A)?

CNGA3 p.Pro48= (c.144G>A) is associated with achromatopsia 2 (ClinVar).

How common is CNGA3 p.Pro48= (c.144G>A) in the general population?

CNGA3 p.Pro48= (c.144G>A) is ultra-rare (popmax 0.0897%, mid) (gnomAD).

How is Achromatopsia inherited?

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

CNGA3 p.Pro48=

c.144G>A · rs199670952 · VCV896736

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0897%, mid)

Conditions

achromatopsia 2

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 -0.58	GERP -3.3
Overall
CADD	4.242	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0897% Middle Eastern · 5/5,572 alleles

Filtering AF 0.0723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.0093% 150/1,613,400 alleles · ultra-rare exomes 141/1,461,070 · genomes 9/152,330 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0897%	1,114
South Asian	0.0879%	1,137
Remaining individualsnot grpmax-eligible	0.0176%	5,677
Admixed American	0.005%	20,005
European (non-Finnish)	0.00424%	23,600
African / African-American	0.00133%	75,018

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.Pro48=
Coding: c.144G>A
MANE Select: NM_001298
dbSNP: rs199670952
Type: single nucleotide variant
Location: chr2:98377729 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 48: a UniProt-annotated variant site (in)

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.Pro48Leu Benign/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
CNGA3 p.Arg223Trp 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-pro48 (accessed [today's date]).

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