Is CSF3R p.Glu680Gln (c.2038G>C) pathogenic?

CSF3R p.Glu680Gln (c.2038G>C) is classified Uncertain significance in CSF3R (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.125); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CSF3R p.Glu680Gln (c.2038G>C)?

CSF3R p.Glu680Gln (c.2038G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CSF3R p.Glu680Gln (c.2038G>C) in the general population?

CSF3R p.Glu680Gln (c.2038G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CSF3R p.Glu680Gln (c.2038G>C)?

AlphaMissense predicts likely benign (score 0.125) — an in-silico prediction, not a clinical call.

CSF3R p.Glu680Gln

c.2038G>C · VCV4234838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.125	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 3.4e-07 · regional, not allelic
Overall
CADD	19.25	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,030 alleles

Overall 6.84e-05% 1/1,461,786 alleles · very rare

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.Glu680Gln
Coding: c.2038G>C
MANE Select: NM_000760
Type: single nucleotide variant
Location: chr1:36467232 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSF3R p.Glu680Lys Uncertain significance ★ ⚠ same residue
CSF3R p.Ala33Asp Uncertain significance ★★ ⚠ same condition
CSF3R p.Ala778Val Uncertain significance ★★ ⚠ same condition
CSF3R p.Arg269Cys Uncertain significance ★★ ⚠ same condition
CSF3R p.Arg428Gly Uncertain significance ★★ ⚠ same condition
CSF3R p.Asp732Asn Uncertain significance ★★ ⚠ same condition
CSF3R p.Cys187Gly Uncertain significance ★★ ⚠ same condition
CSF3R p.Glu84Ala Uncertain significance ★★ ⚠ 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-glu680gln (accessed [today's date]).

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