GFAP p.Arg416=
c.1246C>A · rs121909717 · VCV1568605
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.156%, 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 4.2 | GERP -0.55, phastCons 1 |
| Overall | ||
| CADD | 13.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.156%
African / African-American · 117/74,836 alleles
Filtering AF
0.133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.125%
Overall
0.00835%
134/1,605,184 alleles · rare
exomes 80/1,452,982 · genomes 54/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.156% | 640 |
| Admixed American | 0.0184% | 5,448 |
| Remaining individualsnot grpmax-eligible | 0.00804% | 12,438 |
| European (non-Finnish) | 8.53e-05% | 1,172,163 |
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.Arg416=
- Coding
- c.1246C>A
- MANE Select
- NM_002055
- dbSNP
- rs121909717
- Type
- single nucleotide variant
- Location
- chr17:44908075 (GRCh38)
- Gene constraint
- LOEUF 0.991 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.70 · 1 PDB
- Residue 416
- the 'tail' region; a modified residue (citrulline); a UniProt-annotated variant site (in alxdrd)
Similar variants
- GFAP p.Arg416Trp Pathogenic ★★ same residue
- GFAP p.Arg416Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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.Arg70Trp 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-arg416 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown