Is CNGA3 p.Thr66= (c.198C>T) pathogenic?

CNGA3 p.Thr66= (c.198C>T) is classified Conflicting classifications of pathogenicity in CNGA3 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-14). Rare (popmax 0.243%, nfe); Associated with achromatopsia 2.

What condition is associated with CNGA3 p.Thr66= (c.198C>T)?

CNGA3 p.Thr66= (c.198C>T) is associated with achromatopsia 2 (ClinVar).

How common is CNGA3 p.Thr66= (c.198C>T) in the general population?

CNGA3 p.Thr66= (c.198C>T) is rare (popmax 0.243%, nfe) (gnomAD).

How is Achromatopsia inherited?

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

CNGA3 p.Thr66=

c.198C>T · rs139544302 · VCV257962

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.243%, nfe)

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 -3.3	GERP -3.1
Overall
CADD	3.253	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.243% European (non-Finnish) · 2,870/1,179,606 alleles

Filtering AF 0.236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.233%

Overall 0.202% 3,260/1,611,346 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.301%	332
European (non-Finnish)grpmax	0.243%	411
Remaining individualsnot grpmax-eligible	0.151%	663
Admixed American	0.0801%	1,248
Middle Eastern	0.0406%	2,462
African / African-American	0.0387%	2,585
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,286
East Asian	0.0223%	4,486
South Asian	0.00663%	15,090

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.Thr66=
Coding: c.198C>T
MANE Select: NM_001298
dbSNP: rs139544302
Type: single nucleotide variant
Location: chr2:98377783 (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 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-thr66 (accessed [today's date]).

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