Is CNGA1 p.Tyr330Cys (c.989A>G) pathogenic?

CNGA1 p.Tyr330Cys (c.989A>G) is classified Uncertain significance in CNGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely pathogenic (0.9339); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with CNGA1 p.Tyr330Cys (c.989A>G)?

CNGA1 p.Tyr330Cys (c.989A>G) is associated with inherited retinal dystrophy (ClinVar).

How common is CNGA1 p.Tyr330Cys (c.989A>G) in the general population?

CNGA1 p.Tyr330Cys (c.989A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNGA1 p.Tyr330Cys (c.989A>G)?

AlphaMissense predicts likely pathogenic (score 0.9339) — an in-silico prediction, not a clinical call.

CNGA1 p.Tyr330Cys

c.989A>G · rs2475751463 · VCV3027675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9339 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9339	likely pathogenic
REVEL	0.977	strongly pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 4.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Y334C vs ClinVar Y330C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNGA1
Protein: p.Tyr330Cys
Coding: c.989A>G
MANE Select: NM_001379270
dbSNP: rs2475751463
Type: single nucleotide variant
Location: chr4:47937493 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB
Residue 330: the 'ion conduction pathway' region

Full CNGA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNGA1 p.Arg214Ter Pathogenic ★★ same condition
CNGA1 p.Arg28Ter Pathogenic ★★ same condition
CNGA1 p.Arg420Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Arg510Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Ser316Phe Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Asp500Gly Uncertain significance ★★ ⚠ same condition
CNGA1 p.Gly218Asp Uncertain significance ★★ ⚠ same condition
CNGA1 p.Thr656Ile Uncertain significance ★★ 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/cnga1-p-tyr330cys (accessed [today's date]).

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