Is CSF1R p.His98= (c.294C>T) pathogenic?

CSF1R p.His98= (c.294C>T) is classified Benign in CSF1R (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 21.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with leukoencephalopathy, hereditary diffuse, with spheroids.

What condition is associated with CSF1R p.His98= (c.294C>T)?

CSF1R p.His98= (c.294C>T) is associated with leukoencephalopathy, hereditary diffuse, with spheroids (ClinVar).

CSF1R p.His98=

Q: How common is CSF1R p.His98= (c.294C>T) in the general population?

CSF1R p.His98= (c.294C>T) is common (popmax 21.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.294C>T · rs17652007 · VCV352171

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 21.2%, eas) — too common for a highly-penetrant pathogenic allele

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 2.1	GERP -0.31, phastCons 1
Overall
CADD	6.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.2% East Asian · 9,496/44,850 alleles

Filtering AF 20.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.7%

Overall 2.12% 34,178/1,613,990 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	21.2%	5
Admixed American	20.8%	5
Remaining individualsnot grpmax-eligible	2.81%	36
Finnishnot grpmax-eligible	2.68%	37
African / African-American	2.57%	39
South Asian	1.17%	85
Ashkenazi Jewishnot grpmax-eligible	0.554%	181
European (non-Finnish)	0.469%	213
Middle Eastern	0.314%	319

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.His98=
Coding: c.294C>T
MANE Select: NM_001288705
dbSNP: rs17652007
Type: single nucleotide variant
Location: chr5:150080780 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 98: a β-strand; 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

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-his98 (accessed [today's date]).

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