Is CSF1R p.Ser65= (c.195C>T) pathogenic?

CSF1R p.Ser65= (c.195C>T) is classified Conflicting classifications of pathogenicity in CSF1R (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-29). Very rare (popmax 0.00271%, nfe); Associated with leukoencephalopathy, hereditary diffuse, with spheroids.

What condition is associated with CSF1R p.Ser65= (c.195C>T)?

CSF1R p.Ser65= (c.195C>T) is associated with leukoencephalopathy, hereditary diffuse, with spheroids (ClinVar).

How common is CSF1R p.Ser65= (c.195C>T) in the general population?

CSF1R p.Ser65= (c.195C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

CSF1R p.Ser65=

c.195C>T · rs1758508357 · VCV907498

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Conditions

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 -0.1	GERP -1.2
Overall
CADD	1.644	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,180,032 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00226% 33/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,876
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Ser65=
Coding: c.195C>T
MANE Select: NM_001288705
dbSNP: rs1758508357
Type: single nucleotide variant
Location: chr5:150080879 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 65: a disulfide bond; the ig-like c2-type 1 domain; a β-strand

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.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
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-ser65 (accessed [today's date]).

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