Is CNGA3 p.Pro372= (c.1116C>T) pathogenic?

CNGA3 p.Pro372= (c.1116C>T) is classified Conflicting classifications of pathogenicity in CNGA3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.347%, mid); Associated with achromatopsia 2.

What condition is associated with CNGA3 p.Pro372= (c.1116C>T)?

CNGA3 p.Pro372= (c.1116C>T) is associated with achromatopsia 2 (ClinVar).

How common is CNGA3 p.Pro372= (c.1116C>T) in the general population?

CNGA3 p.Pro372= (c.1116C>T) is rare (popmax 0.347%, mid) (gnomAD).

How is Achromatopsia inherited?

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

CNGA3 p.Pro372=

c.1116C>T · rs201649850 · VCV722716

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.347%, 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 -15	GERP -3.7
Overall
CADD	0.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.347% Middle Eastern · 21/6,048 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.0276% 444/1,610,782 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.347%	288
Admixed American	0.0919%	1,088
Remaining individualsnot grpmax-eligible	0.0369%	2,710
European (non-Finnish)	0.0273%	3,657
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,219
African / African-American	0.016%	6,238
South Asian	0.0033%	30,327
Finnishnot grpmax-eligible	0.00156%	63,964

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.Pro372=
Coding: c.1116C>T
MANE Select: NM_001298
dbSNP: rs201649850
Type: single nucleotide variant
Location: chr2:98396286 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 372: an α-helix; the 'ion conduction pathway' region; a UniProt-annotated variant site (in achm2)

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.Pro372Ser Pathogenic ★★ same residue
CNGA3 p.Pro372Leu Pathogenic ★ same residue
CNGA3 p.Pro372Ala Likely pathogenic 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

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-pro372 (accessed [today's date]).

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