Is CSF3R p.Lys705= (c.2115G>A) pathogenic?

CSF3R p.Lys705= (c.2115G>A) is classified Likely benign in CSF3R (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-13). Very rare (popmax 0.0011%, sas); Associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency.

What condition is associated with CSF3R p.Lys705= (c.2115G>A)?

CSF3R p.Lys705= (c.2115G>A) is associated with autosomal recessive severe congenital neutropenia due to CSF3R deficiency (ClinVar).

How common is CSF3R p.Lys705= (c.2115G>A) in the general population?

CSF3R p.Lys705= (c.2115G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

CSF3R p.Lys705=

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.2115G>A · rs373095416 · VCV2724456

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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	0.034	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.51, phastCons 0.99
Overall
CADD	2.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,094 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,094
European (non-Finnish)	0.000763%	131,116

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.Lys705=
Coding: c.2115G>A
MANE Select: NM_000760
dbSNP: rs373095416
Type: single nucleotide variant
Location: chr1:36466753 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB

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

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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
CSF3R p.Trp547Ter 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-lys705 (accessed [today's date]).

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