Is CNGA1 p.Glu645Ala (c.1934A>C) pathogenic?

CNGA1 p.Glu645Ala (c.1934A>C) is classified Conflicting classifications of pathogenicity in CNGA1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.261); Ultra-rare (popmax 0.0534%, afr); Associated with Inborn genetic diseases.

What condition is associated with CNGA1 p.Glu645Ala (c.1934A>C)?

CNGA1 p.Glu645Ala (c.1934A>C) is associated with Inborn genetic diseases, retinitis pigmentosa 49 (ClinVar).

How common is CNGA1 p.Glu645Ala (c.1934A>C) in the general population?

CNGA1 p.Glu645Ala (c.1934A>C) is ultra-rare (popmax 0.0534%, afr) (gnomAD).

What do computational predictors say about CNGA1 p.Glu645Ala (c.1934A>C)?

AlphaMissense predicts likely benign (score 0.261) — an in-silico prediction, not a clinical call.

CNGA1 p.Glu645Ala

c.1934A>C · rs376378429 · VCV964383

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.261 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.261	likely benign
REVEL	0.393	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E649A vs ClinVar E645A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0534% African / African-American · 40/74,930 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.00266% 43/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0534%	1,873
Remaining individualsnot grpmax-eligible	0.0048%	20,829

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: CNGA1
Protein: p.Glu645Ala
Coding: c.1934A>C
MANE Select: NM_001379270
dbSNP: rs376378429
Type: single nucleotide variant
Location: chr4:47936548 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB
Residue 645: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 49

Similar variants

CNGA1 c.107+2T>G Likely pathogenic ★★ same condition
CNGA1 c.545+2T>A Likely pathogenic ★★ same condition
CNGA1 c.546-1G>C Pathogenic/Likely pathogenic ★★ same condition
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.Arg625Ter 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/cnga1-p-glu645ala (accessed [today's date]).

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