Is CSF3R p.Cys46Phe (c.137_138delinsTT) pathogenic?

CSF3R p.Cys46Phe (c.137138delinsTT) is classified Uncertain significance in CSF3R (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Absent from gnomAD; Associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency.

What condition is associated with CSF3R p.Cys46Phe (c.137_138delinsTT)?

CSF3R p.Cys46Phe (c.137_138delinsTT) is associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency (ClinVar).

How common is CSF3R p.Cys46Phe (c.137_138delinsTT) in the general population?

CSF3R p.Cys46Phe (c.137_138delinsTT) is absent from gnomAD (gnomAD).

CSF3R p.Cys46Phe

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.137_138delinsTT · rs2521830774 · VCV2794048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -1.7, phastCons 0.83
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 3.4e-07 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CSF3R
Protein: p.Cys46Phe
Coding: c.137_138delinsTT
MANE Select: NM_000760
dbSNP: rs2521830774
Type: Indel
Location: chr1:36475600 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB
Residue 46: a disulfide bond; a β-strand; the ig-like c2-type 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

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CSF3R p.Ser471Lys Uncertain significance ★★ same condition
CSF3R p.Pro215_Leu217delinsTer Pathogenic ★ same condition
CSF3R p.Ala520Asn Uncertain significance ★ same condition
CSF3R p.Ala832Lys Uncertain significance ★ same condition
CSF3R p.Glu450Met Uncertain significance ★ same condition
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

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-cys46phe (accessed [today's date]).

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