Is CSF3R p.Glu149Asp (c.447G>C) pathogenic?

CSF3R p.Glu149Asp (c.447G>C) is classified Conflicting classifications of pathogenicity in CSF3R (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-04-08). AlphaMissense: likely benign (0.0729); Rare (popmax 0.53%, nfe); Associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency.

What condition is associated with CSF3R p.Glu149Asp (c.447G>C)?

CSF3R p.Glu149Asp (c.447G>C) is associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency (ClinVar).

How common is CSF3R p.Glu149Asp (c.447G>C) in the general population?

CSF3R p.Glu149Asp (c.447G>C) is rare (popmax 0.53%, nfe) (gnomAD).

What do computational predictors say about CSF3R p.Glu149Asp (c.447G>C)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

CSF3R p.Glu149Asp

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.447G>C · rs139332126 · VCV434837

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.53%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -5.31	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 0.32	GERP -3.2, phastCons 0.72
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 3.4e-07 · regional, not allelic
Overall
CADD	4.535	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

Grpmax group 0.53% European (non-Finnish) · 6,259/1,180,052 alleles

Filtering AF 0.519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.515%

Overall 0.439% 7,085/1,614,236 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.53%	189
Remaining individualsnot grpmax-eligible	0.472%	212
Middle Eastern	0.297%	337
Ashkenazi Jewishnot grpmax-eligible	0.294%	340
South Asian	0.234%	428
Admixed American	0.183%	546
African / African-American	0.0893%	1,120
Finnishnot grpmax-eligible	0.0562%	1,779

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: CSF3R
Protein: p.Glu149Asp
Coding: c.447G>C
MANE Select: NM_000760
dbSNP: rs139332126
Type: single nucleotide variant
Location: chr1:36473802 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB
Residue 149: the fibronectin type-iii 1 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.Glu149Lys Uncertain significance ★★ ⚠ same residue
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.Thr618Ile 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/csf3r-p-glu149asp (accessed [today's date]).

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