Is CNGA3 p.Asp24= (c.72T>C) pathogenic?

CNGA3 p.Asp24= (c.72T>C) is classified Benign in CNGA3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 18.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with achromatopsia 2.

What condition is associated with CNGA3 p.Asp24= (c.72T>C)?

CNGA3 p.Asp24= (c.72T>C) is associated with achromatopsia 2 (ClinVar).

How is Achromatopsia inherited?

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

CNGA3 p.Asp24=

Q: How common is CNGA3 p.Asp24= (c.72T>C) in the general population?

CNGA3 p.Asp24= (c.72T>C) is common (popmax 18.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.72T>C · rs6727412 · VCV257964

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 18.4%, nfe) — too common for a highly-penetrant pathogenic allele

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 -1.7	GERP -2.5
Overall
CADD	0.527	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.4% European (non-Finnish) · 216,828/1,179,362 alleles

Filtering AF 18.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.3%

Overall 16.1% 260,500/1,613,068 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	18.4%	5
Remaining individualsnot grpmax-eligible	15.2%	7
Middle Eastern	13.6%	7
Ashkenazi Jewishnot grpmax-eligible	13.5%	7
Admixed American	11.6%	9
Finnishnot grpmax-eligible	10.3%	10
African / African-American	9.74%	10
South Asian	9.03%	11
Amishnot grpmax-eligible	8.79%	11
East Asian	0.455%	220

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.Asp24=
Coding: c.72T>C
MANE Select: NM_001298
dbSNP: rs6727412
Type: single nucleotide variant
Location: chr2:98370047 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 24: the 'disordered' region

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 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
CNGA3 p.Arg23Ter 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-asp24 (accessed [today's date]).

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