GPT2 p.Pro392=
c.1176G>T · rs35148330 · VCV734196
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.346%, afr)
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 -11 | GERP -3.5 |
| Overall | ||
| CADD | 0.126 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.346%
African / African-American · 260/75,052 alleles
Filtering AF
0.312%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.298%
Overall
0.0216%
349/1,613,568 alleles · rare
exomes 189/1,461,232 · genomes 160/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.346% | 289 |
| Admixed American | 0.0501% | 1,996 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,083 |
| Middle Eastern | 0.0165% | 6,054 |
| South Asian | 0.0132% | 7,586 |
| European (non-Finnish) | 0.00136% | 73,743 |
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
- GPT2
- Protein
- p.Pro392=
- Coding
- c.1176G>T
- MANE Select
- NM_133443
- dbSNP
- rs35148330
- Type
- single nucleotide variant
- Location
- chr16:46922380 (GRCh38)
- Gene constraint
- LOEUF 0.677 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.89 · 1 PDB
Similar variants
- GPT2 p.Pro392Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- GPT2 p.Arg92Ter Pathogenic/Likely pathogenic ★★ same type
- GPT2 p.Arg110Trp Uncertain significance ★★ ⚠ same type
- GPT2 p.Gly324Glu Uncertain significance ★★ ⚠ same type
- GPT2 p.Ile197Val Uncertain significance ★★ ⚠ same type
- GPT2 p.Phe446Ser Uncertain significance ★★ ⚠ same type
- GPT2 p.Ser124Thr Uncertain significance ★★ ⚠ same type
- GPT2 p.Tyr182Phe 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/gpt2-p-pro392 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown