Is CSF1R p.Asn240Ser (c.719A>G) pathogenic?

CSF1R p.Asn240Ser (c.719A>G) is classified Uncertain significance in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). AlphaMissense: likely benign (0.0734); Very rare (popmax 0.000339%, nfe); Associated with leukoencephalopathy, diffuse hereditary, with spheroids 1.

What condition is associated with CSF1R p.Asn240Ser (c.719A>G)?

CSF1R p.Asn240Ser (c.719A>G) is associated with leukoencephalopathy, diffuse hereditary, with spheroids 1, brain abnormalities, neurodegeneration, and dysosteosclerosis (ClinVar).

How common is CSF1R p.Asn240Ser (c.719A>G) in the general population?

CSF1R p.Asn240Ser (c.719A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CSF1R p.Asn240Ser (c.719A>G)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

CSF1R p.Asn240Ser

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.719A>G · VCV3591897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukoencephalopathy, diffuse hereditary, with spheroids 1

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -1.3, phastCons 0.63
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	13.7	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,962 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,828 alleles · very rare

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.Asn240Ser
Coding: c.719A>G
MANE Select: NM_001288705
Type: single nucleotide variant
Location: chr5:150078122 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 240: a disulfide bond; the ig-like c2-type 3 domain

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

Also linked: brain abnormalities, neurodegeneration, and dysosteosclerosis

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

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

CSF1R p.Asn240Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
CSF1R p.Ala780Val Likely pathogenic ★★ same condition
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.Gln481Ter Pathogenic ★★ same condition
CSF1R p.Glu633Lys 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-asn240ser (accessed [today's date]).

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