Is CNGA3 p.Ser401Pro (c.1201T>C) pathogenic?

CNGA3 p.Ser401Pro (c.1201T>C) is classified Pathogenic in CNGA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-18). AlphaMissense: likely pathogenic (0.9886); Very rare (popmax 8.48e-05%, nfe); Associated with achromatopsia 2.

What condition is associated with CNGA3 p.Ser401Pro (c.1201T>C)?

CNGA3 p.Ser401Pro (c.1201T>C) is associated with achromatopsia 2 (ClinVar).

How common is CNGA3 p.Ser401Pro (c.1201T>C) in the general population?

CNGA3 p.Ser401Pro (c.1201T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Achromatopsia inherited?

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

What do computational predictors say about CNGA3 p.Ser401Pro (c.1201T>C)?

AlphaMissense predicts likely pathogenic (score 0.9886) — an in-silico prediction, not a clinical call.

CNGA3 p.Ser401Pro

c.1201T>C · rs916035276 · VCV1444626

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

achromatopsia 2

Computational evidence

Protein change
AlphaMissense	0.9886	likely pathogenic ✓ concordant with ClinVar · top 3% in CNGA3
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -14.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,336 bp · p 0.34 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,710 alleles

Overall 6.84e-05% 1/1,461,398 alleles · very rare

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.Ser401Pro
Coding: c.1201T>C
MANE Select: NM_001298
dbSNP: rs916035276
Type: single nucleotide variant
Location: chr2:98396371 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 401: 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 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-ser401pro (accessed [today's date]).

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