Is CSF1R p.Ala780Val (c.2339C>T) pathogenic?

CSF1R p.Ala780Val (c.2339C>T) is classified Likely pathogenic in CSF1R (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-03-30). AlphaMissense: likely pathogenic (0.9956); Absent from gnomAD v4.1; Associated with leukoencephalopathy, diffuse hereditary, with spheroids 1.

What condition is associated with CSF1R p.Ala780Val (c.2339C>T)?

CSF1R p.Ala780Val (c.2339C>T) is associated with leukoencephalopathy, diffuse hereditary, with spheroids 1 (ClinVar).

How common is CSF1R p.Ala780Val (c.2339C>T) in the general population?

CSF1R p.Ala780Val (c.2339C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF1R p.Ala780Val (c.2339C>T)?

AlphaMissense predicts likely pathogenic (score 0.9956) — an in-silico prediction, not a clinical call.

CSF1R p.Ala780Val

Q: How is Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2339C>T · rs2113779595 · VCV3068555

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukoencephalopathy, diffuse hereditary, with spheroids 1

Computational evidence

Protein change
AlphaMissense	0.9956	likely pathogenic ✓ concordant with ClinVar · top 4% in CSF1R
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -12.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 2,952 bp · p 1.2e-16 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSF1R
Protein: p.Ala780Val
Coding: c.2339C>T
MANE Select: NM_001288705
dbSNP: rs2113779595
Type: single nucleotide variant
Location: chr5:150056322 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 780: the protein kinase domain; a UniProt-annotated variant site (in banddos); a UniProt-annotated variant site (in hdls1)

Full CSF1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

leukoencephalopathy, diffuse hereditary, with spheroids 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

CSF1R p.Ala780Pro Uncertain significance ★ ⚠ same residue
CSF1R p.Ala780Thr Uncertain significance ★ ⚠ same residue
CSF1R p.Arg676Ter Pathogenic ★★ same condition
CSF1R p.Arg777Gln Pathogenic ★★ same condition
CSF1R p.Arg782Cys Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Arg782His Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Glu633Lys Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Gly589Arg Pathogenic/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-ala780val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown