Is CSF1R p.Pro962= (c.2886C>T) pathogenic?

CSF1R p.Pro962= (c.2886C>T) is classified Conflicting classifications of pathogenicity in CSF1R (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-25). Very rare (popmax 0.00339%, nfe); Associated with leukoencephalopathy, hereditary diffuse, with spheroids.

How common is CSF1R p.Pro962= (c.2886C>T) in the general population?

CSF1R p.Pro962= (c.2886C>T) is very rare (popmax 0.00339%, nfe) (gnomAD).

CSF1R p.Pro962=

Q: What condition is associated with CSF1R p.Pro962= (c.2886C>T)?

CSF1R p.Pro962= (c.2886C>T) is associated with leukoencephalopathy, hereditary diffuse, with spheroids, CSF1R-related disorder (ClinVar).

c.2886C>T · rs370648666 · VCV352122

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00339%, 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 0.021	GERP -3.9, phastCons 0.48
Overall
CADD	4.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% European (non-Finnish) · 40/1,180,046 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00248% 40/1,614,056 alleles · very rare

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.Pro962=
Coding: c.2886C>T
MANE Select: NM_001288705
dbSNP: rs370648666
Type: single nucleotide variant
Location: chr5:150054102 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 962: 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

Also linked: CSF1R-related disorder

Similar variants

CSF1R p.Pro962Leu Uncertain significance ★ ⚠ same residue
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

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-pro962 (accessed [today's date]).

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