Is CSF1R p.Ser730Pro (c.2188T>C) pathogenic?

CSF1R p.Ser730Pro (c.2188T>C) is classified Uncertain significance in CSF1R (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-07). AlphaMissense: likely benign (0.1104); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CSF1R p.Ser730Pro (c.2188T>C)?

CSF1R p.Ser730Pro (c.2188T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CSF1R p.Ser730Pro (c.2188T>C) in the general population?

CSF1R p.Ser730Pro (c.2188T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CSF1R p.Ser730Pro (c.2188T>C)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

CSF1R p.Ser730Pro

c.2188T>C · rs1379743229 · VCV1357243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.96, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,496 bp · p 0.56 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000205% 3/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Ser730Pro
Coding: c.2188T>C
MANE Select: NM_001288705
dbSNP: rs1379743229
Type: single nucleotide variant
Location: chr5:150057537 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 730: the protein kinase domain; a UniProt-annotated variant site (in banddos)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSF1R p.Ser730= Likely benign ★ same residue
CSF1R p.Ala299Val Uncertain significance ★★ ⚠ same condition
CSF1R p.Ala770Thr Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg41Gln Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg549Cys Uncertain significance ★★ ⚠ same condition
CSF1R p.Arg710Cys Uncertain significance ★★ ⚠ same condition
CSF1R p.Gln173Arg Uncertain significance ★★ ⚠ same condition
CSF1R p.Glu628Ala Uncertain significance ★★ ⚠ 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-ser730pro (accessed [today's date]).

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