Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 24.1%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.79 | GERP 0.59, phastCons 0.002 |
| Overall | ||
| CADD | 9.208 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
24.1%
African / African-American · 18,042/75,018 alleles
Filtering AF
23.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 23.6%
Overall
12.4%
199,782/1,613,652 alleles · common
exomes 178,094/1,461,358 · genomes 21,688/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 24.1% | 4 |
| East Asian | 14.7% | 7 |
| European (non-Finnish) | 12.6% | 8 |
| Amishnot grpmax-eligible | 12% | 8 |
| Remaining individualsnot grpmax-eligible | 11.2% | 9 |
| South Asian | 8.88% | 11 |
| Ashkenazi Jewishnot grpmax-eligible | 7.87% | 13 |
| Admixed American | 7.15% | 14 |
| Finnishnot grpmax-eligible | 6.9% | 14 |
| Middle Eastern | 4.81% | 21 |
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
- GFAP
- Protein
- p.Arg286=
- Coding
- c.858G>A
- MANE Select
- NM_002055
- dbSNP
- rs2289681
- Type
- single nucleotide variant
- Location
- chr17:44911720 (GRCh38)
- Gene constraint
- LOEUF 0.991 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.70 · 1 PDB
- Residue 286
- the if rod domain; the 'coil 2b' region
Similar variants
- GFAP p.Arg239Cys Pathogenic ★★ same type
- GFAP p.Arg239His Pathogenic ★★ same type
- GFAP p.Arg239Leu Pathogenic ★★ same type
- GFAP p.Arg258Cys Pathogenic ★★ ⚠ same type
- GFAP p.Arg376Trp Pathogenic ★★ same type
- GFAP p.Arg416Trp Pathogenic ★★ same type
- GFAP p.Arg70Trp Pathogenic ★★ same type
- GFAP p.Arg79Cys 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/gfap-p-arg286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown