Is CSF1R p.Ser688fs (c.2060dup) pathogenic?

CSF1R p.Ser688fs (c.2060dup) is classified Pathogenic in CSF1R (ClinVar, No assertion criteria, 2 submitters; last evaluated 2014-01-14). Absent from gnomAD; Associated with leukoencephalopathy, hereditary diffuse, with spheroids.

What condition is associated with CSF1R p.Ser688fs (c.2060dup)?

CSF1R p.Ser688fs (c.2060dup) is associated with leukoencephalopathy, hereditary diffuse, with spheroids (ClinVar).

How common is CSF1R p.Ser688fs (c.2060dup) in the general population?

CSF1R p.Ser688fs (c.2060dup) is absent from gnomAD (gnomAD).

CSF1R p.Ser688fs

c.2060dup · rs587777245 · VCV120322

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

leukoencephalopathy, hereditary diffuse, with spheroids

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 2.3, phastCons 0.93

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CSF1R
Protein: p.Ser688fs
Coding: c.2060dup
MANE Select: NM_001288705
dbSNP: rs587777245
Type: Duplication
Location: chr5:150059771 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 688: the protein kinase domain; a UniProt-annotated variant site (in banddos)

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

Disease context

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

Similar variants

CSF1R p.Phe971fs Uncertain significance ★★ same condition
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-ser688fs (accessed [today's date]).

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