CSF1R p.Val468=
c.1404G>A · rs201654254 · VCV352151
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0317%, amr)
Conditions
1
leukoencephalopathy, hereditary diffuse, with spheroids
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 -0.14 | GERP -4.7, phastCons 0.053 |
| Overall | ||
| CADD | 3.332 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0317%
Admixed American · 19/60,026 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.00663%
107/1,614,176 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0317% | 3,159 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.016% | 6,254 |
| European (non-Finnish) | 0.00525% | 19,032 |
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
- CSF1R
- Protein
- p.Val468=
- Coding
- c.1404G>A
- MANE Select
- NM_001288705
- dbSNP
- rs201654254
- Type
- single nucleotide variant
- Location
- chr5:150069979 (GRCh38)
- Gene constraint
- LOEUF 0.485 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 78.08 · 26 PDB
- Residue 468
- a β-strand; a disulfide bond; the ig-like c2-type 5 domain
Similar variants
- CSF1R p.Val468Leu Uncertain significance ★★ ⚠ same residue
- CSF1R p.Ala781Val Pathogenic ★★ same condition
- CSF1R p.Arg777Gln Pathogenic ★★ same condition
- CSF1R p.Arg777Trp Pathogenic/Likely pathogenic ★★ same condition
- CSF1R p.Arg782Cys Pathogenic/Likely pathogenic ★★ same condition
- CSF1R p.Arg782His Pathogenic/Likely pathogenic ★★ same condition
- CSF1R p.Gln481Ter Pathogenic ★★ same condition
- CSF1R p.Gln877Ter Likely pathogenic ★★ same condition
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/csf1r-p-val468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown