Is CNGA3 p.Ser542= (c.1626C>T) pathogenic?

CNGA3 p.Ser542= (c.1626C>T) is classified Benign in CNGA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Common (popmax 6.32%, eas) — too common for a highly-penetrant pathogenic allele; Associated with achromatopsia 2.

What condition is associated with CNGA3 p.Ser542= (c.1626C>T)?

CNGA3 p.Ser542= (c.1626C>T) 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.Ser542=

Q: How common is CNGA3 p.Ser542= (c.1626C>T) in the general population?

CNGA3 p.Ser542= (c.1626C>T) is common (popmax 6.32%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1626C>T · rs78583671 · VCV337663

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.32%, eas) — 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 -8.5	GERP -3.7
Overall
CADD	1.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.32% East Asian · 2,835/44,878 alleles

Filtering AF 6.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.04%

Overall 0.246% 3,965/1,614,166 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	6.32%	16
Remaining individualsnot grpmax-eligible	0.485%	206
Finnishnot grpmax-eligible	0.419%	239
Ashkenazi Jewishnot grpmax-eligible	0.213%	470
South Asian	0.134%	747
Middle Eastern	0.0825%	1,212
Admixed American	0.0566%	1,766
European (non-Finnish)	0.0269%	3,711
African / African-American	0.0227%	4,414

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.Ser542=
Coding: c.1626C>T
MANE Select: NM_001298
dbSNP: rs78583671
Type: single nucleotide variant
Location: chr2:98396796 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 542: the 'cyclic nucleotide-binding domain' 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-ser542 (accessed [today's date]).

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