Is CSF1R p.Pro247Leu (c.740C>T) pathogenic?

CSF1R p.Pro247Leu (c.740C>T) is classified Uncertain significance in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-19). AlphaMissense: likely benign (0.0866); Absent from gnomAD v4.1; Associated with brain abnormalities, neurodegeneration, and dysosteosclerosis.

What condition is associated with CSF1R p.Pro247Leu (c.740C>T)?

CSF1R p.Pro247Leu (c.740C>T) is associated with brain abnormalities, neurodegeneration, and dysosteosclerosis (ClinVar).

How common is CSF1R p.Pro247Leu (c.740C>T) in the general population?

CSF1R p.Pro247Leu (c.740C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF1R p.Pro247Leu (c.740C>T)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

CSF1R p.Pro247Leu

c.740C>T · rs17855673 · VCV2441972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

brain abnormalities, neurodegeneration, and dysosteosclerosis

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -2.9
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	1.54	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSF1R
Protein: p.Pro247Leu
Coding: c.740C>T
MANE Select: NM_001288705
dbSNP: rs17855673
Type: single nucleotide variant
Location: chr5:150077425 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 247: a disulfide bond; the ig-like c2-type 3 domain

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

Disease context

brain abnormalities, neurodegeneration, and dysosteosclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSF1R p.Arg782His Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Gln481Ter Pathogenic ★★ same condition
CSF1R p.Tyr540Ter Pathogenic ★★ same condition
CSF1R c.1859-119G>A Uncertain significance ★★ same condition
CSF1R p.Ala770Thr Uncertain significance ★★ ⚠ same condition
CSF1R p.Val117Met Uncertain significance ★★ ⚠ same condition
CSF1R p.Val468Leu Uncertain significance ★★ ⚠ same condition
CSF1R c.1510+16C>T Benign ★★ 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-pro247leu (accessed [today's date]).

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