CNGA3 p.Thr435=
c.1305G>A · rs150008953 · VCV1125567
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, eas)
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 -8.9 | GERP -3.7 |
| Overall | ||
| CADD | 0.165 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,862 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.00217%
35/1,614,002 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,608 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
| African / African-American | 0.004% | 25,006 |
| South Asian | 0.00329% | 30,359 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.00144% | 69,414 |
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.Thr435=
- Coding
- c.1305G>A
- MANE Select
- NM_001298
- dbSNP
- rs150008953
- Type
- single nucleotide variant
- Location
- chr2:98396475 (GRCh38)
- Gene constraint
- LOEUF 1.126 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.33 · 10 PDB
- Residue 435
- an α-helix; the 'c-linker' region
Similar variants
- CNGA3 p.Thr435Met Benign/Likely benign ★★ ⚠ same residue
- CNGA3 c.216-1G>A Likely pathogenic ★★ same type
- CNGA3 c.396-11C>G Pathogenic/Likely pathogenic ★★ same type
- CNGA3 c.450-1G>A Pathogenic ★★ same type
- CNGA3 p.Ala262Pro Likely pathogenic ★★ ⚠ same type
- CNGA3 p.Ala318Thr Pathogenic ★★ same type
- CNGA3 p.Ala469Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- CNGA3 p.Arg129Ter 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/cnga3-p-thr435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown