Is CSF1R p.Ser94= (c.282C>T) pathogenic?

CSF1R p.Ser94= (c.282C>T) is classified Benign/Likely benign in CSF1R (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-04-01). Low-frequency (popmax 1.06%, mid); Associated with leukoencephalopathy, hereditary diffuse, with spheroids.

How common is CSF1R p.Ser94= (c.282C>T) in the general population?

CSF1R p.Ser94= (c.282C>T) is low-frequency (popmax 1.06%, mid) (gnomAD).

CSF1R p.Ser94=

Q: What condition is associated with CSF1R p.Ser94= (c.282C>T)?

CSF1R p.Ser94= (c.282C>T) is associated with leukoencephalopathy, hereditary diffuse, with spheroids, CSF1R-related disorder (ClinVar).

c.282C>T · rs41287102 · VCV352172

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, mid)

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 -11	GERP -3.9
Overall
CADD	0.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.06% Middle Eastern · 64/6,062 alleles

Filtering AF 0.848% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.773%

Overall 0.562% 9,075/1,614,056 alleles · low-frequency exomes 8,325/1,461,760 · genomes 750/152,296 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.33%	75
Middle Easterngrpmax	1.06%	95
Admixed American	0.653%	153
European (non-Finnish)	0.636%	157
Remaining individualsnot grpmax-eligible	0.592%	169
South Asian	0.181%	552
African / African-American	0.141%	708
Finnishnot grpmax-eligible	0.116%	865
East Asian	0.00223%	44,892

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser94=
Coding: c.282C>T
MANE Select: NM_001288705
dbSNP: rs41287102
Type: single nucleotide variant
Location: chr5:150080792 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 94: the ig-like c2-type 1 domain

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

Also linked: CSF1R-related disorder

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.Gln642Ter Pathogenic/Likely 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-ser94 (accessed [today's date]).

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