CNGA1 p.Pro664=
c.1992G>A · VCV4753768
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -1.6 | GERP -7.5 |
| Overall | ||
| CADD | 4.191 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000889%
13/1,461,882 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| South Asian | 0.0022% | 45,537 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,512 |
| European (non-Finnish) | 0.000678% | 147,502 |
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.Pro664=
- Coding
- c.1992G>A
- MANE Select
- NM_001379270
- Type
- single nucleotide variant
- Location
- chr4:47936490 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.88 · 19 PDB
Similar variants
- CNGA1 p.Pro664Leu Uncertain significance ★★ ⚠ same residue
- CNGA1 p.Pro664Thr Uncertain significance ★★ same residue
- CNGA1 p.Pro664Gln Uncertain significance ★ same residue
- CNGA1 c.107+1G>A Likely pathogenic ★★ same type
- CNGA1 c.107+2T>G Likely pathogenic ★★ same type
- CNGA1 c.545+2T>A Likely pathogenic ★★ same type
- CNGA1 c.545+2T>C Likely pathogenic ★★ same type
- CNGA1 c.546-1G>C Pathogenic/Likely pathogenic ★★ same type
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-pro664 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown