GNAI3 p.Phe95=
c.285T>C · VCV4807086
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0488%, nfe)
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 2.9 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 12.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0488%
European (non-Finnish) · 575/1,178,842 alleles
Filtering AF
0.0455%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0441%
Overall
0.0373%
601/1,611,856 alleles · ultra-rare
exomes 578/1,459,638 · genomes 23/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0488% | 2,050 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,455 |
| African / African-American | 0.00935% | 10,696 |
| Admixed American | 0.00837% | 11,944 |
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
- GNAI3
- Protein
- p.Phe95=
- Coding
- c.285T>C
- MANE Select
- NM_006496
- Type
- single nucleotide variant
- Location
- chr1:109574019 (GRCh38)
- Gene constraint
- LOEUF 1.113 · pLI 0.17 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 94.03 · 27 PDB
- Residue 95
- the g-alpha domain; an α-helix
Similar variants
- GNAI3 p.Gly40Arg Pathogenic/Likely pathogenic ★★ same type
- GNAI3 p.Gly40Val Likely pathogenic ★★ same type
- GNAI3 p.Ser47Asn Pathogenic/Likely pathogenic ★★ same type
- GNAI3 p.Gly292Cys Uncertain significance ★★ ⚠ same type
- GNAI3 p.Ile49Thr Uncertain significance ★★ ⚠ same type
- GNAI3 p.Lys10Arg Uncertain significance ★★ ⚠ same type
- GNAI3 p.Phe108Leu Uncertain significance ★★ ⚠ same type
- GNAI3 c.591-18T>G Benign ★★ 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/gnai3-p-phe95 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown