Is CSF3R p.Thr618Ile (c.1853C>T) pathogenic?

CSF3R p.Thr618Ile (c.1853C>T) is classified Pathogenic/Likely pathogenic in CSF3R (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-31). AlphaMissense: likely pathogenic (0.6348); Absent from gnomAD v4.1; Associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency.

What condition is associated with CSF3R p.Thr618Ile (c.1853C>T)?

CSF3R p.Thr618Ile (c.1853C>T) is associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency, hereditary neutrophilia, early T cell progenitor acute lymphoblastic leukemia (ClinVar).

How common is CSF3R p.Thr618Ile (c.1853C>T) in the general population?

CSF3R p.Thr618Ile (c.1853C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF3R p.Thr618Ile (c.1853C>T)?

AlphaMissense predicts likely pathogenic (score 0.6348) — an in-silico prediction, not a clinical call.

CSF3R p.Thr618Ile

Q: How is Autosomal recessive severe congenital neutropenia due to CSF3R deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1853C>T · rs796065343 · VCV208339

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6348 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Computational evidence

Protein change
AlphaMissense	0.6348	likely pathogenic ✓ concordant with ClinVar · top 9% in CSF3R
REVEL	0.412	indeterminate
SaProt	LLR -11.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.64, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 3.4e-07 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Chronic Neutrophilic Leukemia	Ruxolitinib	D	Sensitivity/Response
Chronic Neutrophilic Leukemia	Ruxolitinib	C	Sensitivity/Response
Acute Myeloid Leukemia		B	Poor Outcome

Variant & gene context

Gene: CSF3R
Protein: p.Thr618Ile
Coding: c.1853C>T
MANE Select: NM_000760
dbSNP: rs796065343
Type: single nucleotide variant
Location: chr1:36467833 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB
Residue 618: the fibronectin type-iii 5 domain

Full CSF3R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive severe congenital neutropenia due to CSF3R deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neutrophilia early T cell progenitor acute lymphoblastic leukemia

For Autosomal recessive severe congenital neutropenia due to CSF3R deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CSF3R c.1072-1G>A Pathogenic/Likely pathogenic ★★ same condition
CSF3R c.843+2T>C Pathogenic/Likely pathogenic ★★ same condition
CSF3R c.998-2A>T Likely pathogenic ★★ same condition
CSF3R p.Arg308Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CSF3R p.Arg440Ter Pathogenic ★★ same condition
CSF3R p.Gln114Ter Pathogenic/Likely pathogenic ★★ same condition
CSF3R p.Trp547Ter Pathogenic/Likely pathogenic ★★ same condition
CSF3R p.Trp63Ter 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/csf3r-p-thr618ile (accessed [today's date]).

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