Is CSF1R p.Arg782His (c.2345G>A) pathogenic?

CSF1R p.Arg782His (c.2345G>A) is classified Pathogenic/Likely pathogenic in CSF1R (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-22). AlphaMissense: likely pathogenic (0.9927); Absent from gnomAD v4.1; Associated with brain abnormalities, neurodegeneration, and dysosteosclerosis.

What condition is associated with CSF1R p.Arg782His (c.2345G>A)?

CSF1R p.Arg782His (c.2345G>A) is associated with brain abnormalities, neurodegeneration, and dysosteosclerosis, neurodegenerative disease, leukoencephalopathy, hereditary diffuse, with spheroids (ClinVar).

How common is CSF1R p.Arg782His (c.2345G>A) in the general population?

CSF1R p.Arg782His (c.2345G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF1R p.Arg782His (c.2345G>A)?

AlphaMissense predicts likely pathogenic (score 0.9927) — an in-silico prediction, not a clinical call.

CSF1R p.Arg782His

c.2345G>A · rs281860281 · VCV38378

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9927 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

brain abnormalities, neurodegeneration, and dysosteosclerosis

Computational evidence

Protein change
AlphaMissense	0.9927	likely pathogenic ✓ concordant with ClinVar · top 5% in CSF1R
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -16.90	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 2,952 bp · p 1.2e-16 · regional, not allelic
Overall
CADD	27.9	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.Arg782His
Coding: c.2345G>A
MANE Select: NM_001288705
dbSNP: rs281860281
Type: single nucleotide variant
Location: chr5:150056316 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 782: the protein kinase domain; an α-helix; a UniProt-annotated variant site (in banddos); a UniProt-annotated variant site (in hdls1); a UniProt-annotated variant site (in hdls1; impairs autophosphorylation upon stimulation with csf1)

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

Disease context

brain abnormalities, neurodegeneration, and dysosteosclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodegenerative disease leukoencephalopathy, hereditary diffuse, with spheroids leukoencephalopathy, diffuse hereditary, with spheroids 1

Similar variants

CSF1R p.Arg782Cys Pathogenic/Likely pathogenic ★★ same residue
CSF1R p.Arg782Leu Likely pathogenic ★ same residue
CSF1R p.Ala780Val Likely pathogenic ★★ same condition
CSF1R p.Ala781Val Pathogenic ★★ same condition
CSF1R p.Arg676Ter Pathogenic ★★ same condition
CSF1R p.Arg777Gln Pathogenic ★★ same condition
CSF1R p.Arg777Trp Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Gln481Ter 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-arg782his (accessed [today's date]).

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