Is CSF3R p.Ala470= (c.1410G>A) pathogenic?

CSF3R p.Ala470= (c.1410G>A) is classified Benign/Likely benign in CSF3R (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.237%, amr); Associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency.

What condition is associated with CSF3R p.Ala470= (c.1410G>A)?

CSF3R p.Ala470= (c.1410G>A) is associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency (ClinVar).

How common is CSF3R p.Ala470= (c.1410G>A) in the general population?

CSF3R p.Ala470= (c.1410G>A) is rare (popmax 0.237%, amr) (gnomAD).

CSF3R p.Ala470=

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.1410G>A · rs3917988 · VCV256791

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.237%, amr)

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.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -3, phastCons 0.97
Overall
CADD	4.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.237% Admixed American · 142/60,028 alleles

Filtering AF 0.213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.21%

Overall 0.189% 3,048/1,614,202 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.237%	423
European (non-Finnish)	0.22%	454
Remaining individualsnot grpmax-eligible	0.19%	525
Ashkenazi Jewishnot grpmax-eligible	0.179%	559
South Asian	0.109%	920
Middle Eastern	0.066%	1,516
African / African-American	0.0266%	3,753
Finnishnot grpmax-eligible	0.0187%	5,334
East Asian	0.00223%	44,886

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.Ala470=
Coding: c.1410G>A
MANE Select: NM_000760
dbSNP: rs3917988
Type: single nucleotide variant
Location: chr1:36469716 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB
Residue 470: the fibronectin type-iii 4 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.Ala470Val Uncertain significance ★ ⚠ same residue
CSF3R p.Ala470Thr Likely benign ★ 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

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-ala470 (accessed [today's date]).

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