GNAT2 p.Phe215=
c.645C>T · VCV3616307
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0231%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.057 | GERP -4.2, phastCons 0.008 |
| Overall | ||
| CADD | 13.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0231%
South Asian · 21/91,028 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.00242%
39/1,612,036 alleles · ultra-rare
exomes 37/1,459,750 · genomes 2/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0231% | 4,335 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,939 |
| East Asian | 0.00223% | 44,862 |
| European (non-Finnish) | 0.000679% | 147,259 |
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
- GNAT2
- Protein
- p.Phe215=
- Coding
- c.645C>T
- MANE Select
- NM_001377295
- Type
- single nucleotide variant
- Location
- chr1:109606045 (GRCh38)
- Gene constraint
- LOEUF 1.176 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.21 · 2 PDB
- Residue 215
- the g-alpha domain
Similar variants
- GNAT2 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
- GNAT2 p.Arg161Ter Pathogenic ★★ same type
- GNAT2 p.Arg313Ter Pathogenic ★★ same type
- GNAT2 p.Gln58Ter Pathogenic/Likely pathogenic ★★ same type
- GNAT2 c.118+5G>A Uncertain significance ★★ same type
- GNAT2 c.590+6T>C Uncertain significance ★★ same type
- GNAT2 c.-53-78G>A Uncertain significance ★★ same type
- GNAT2 p.Ala152Thr Uncertain significance ★★ ⚠ 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/gnat2-p-phe215 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown