GFAP p.Ala253=
c.759C>T · rs190972724 · VCV66503
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00666%, amr)
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 -3.7 |
| Overall | ||
| CADD | 0.577 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
Admixed American · 4/60,028 alleles
Filtering AF
0.00225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00198%
Overall
0.0026%
42/1,614,198 alleles · very rare
exomes 38/1,461,866 · genomes 4/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00666% | 15,007 |
| European (non-Finnish) | 0.00305% | 32,779 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,512 |
| African / African-American | 0.00133% | 75,054 |
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.Ala253=
- Coding
- c.759C>T
- MANE Select
- NM_002055
- dbSNP
- rs190972724
- Type
- single nucleotide variant
- Location
- chr17:44913290 (GRCh38)
- Gene constraint
- LOEUF 0.991 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.70 · 1 PDB
- Residue 253
- the if rod domain; a UniProt-annotated variant site (in alxdrd; affects intermediate filaments formation yielding protein aggregates); the 'linker 2' region
Similar variants
- GFAP p.Ala253Gly Pathogenic ★ same residue
- GFAP p.Ala253Thr Uncertain significance ★ ⚠ 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.Arg416Trp 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-ala253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown