Is CSF3R p.Ala778Val (c.2333C>T) pathogenic?

CSF3R p.Ala778Val (c.2333C>T) is classified Uncertain significance in CSF3R (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-06). AlphaMissense: likely benign (0.1115); Very rare (popmax 0.00673%, amr); Associated with Inborn genetic diseases.

What condition is associated with CSF3R p.Ala778Val (c.2333C>T)?

CSF3R p.Ala778Val (c.2333C>T) is associated with Inborn genetic diseases, autosomal recessive severe congenital neutropenia due to CSF3R deficiency (ClinVar).

How common is CSF3R p.Ala778Val (c.2333C>T) in the general population?

CSF3R p.Ala778Val (c.2333C>T) is very rare (popmax 0.00673%, amr) (gnomAD).

What do computational predictors say about CSF3R p.Ala778Val (c.2333C>T)?

AlphaMissense predicts likely benign (score 0.1115) — an in-silico prediction, not a clinical call.

CSF3R p.Ala778Val

c.2333C>T · rs759549054 · VCV2485475

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1115 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1115	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.23	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 -0.071	GERP -1.7
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 3.4e-07 · regional, not allelic
Overall
CADD	8.717	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 0.00673% Admixed American · 4/59,442 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000932% 15/1,608,764 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00673%	14,860
African / African-American	0.00267%	37,410
South Asian	0.0022%	45,378
European (non-Finnish)	0.000595%	168,098

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.Ala778Val
Coding: c.2333C>T
MANE Select: NM_000760
dbSNP: rs759549054
Type: single nucleotide variant
Location: chr1:36466535 (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

Also linked: autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Similar variants

CSF3R p.Ala778= Conflicting classifications of pathogenicity ★ same residue
CSF3R p.Ala778Glu 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

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-ala778val (accessed [today's date]).

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