Is CSF3R p.Pro148Ser (c.442C>T) pathogenic?

CSF3R p.Pro148Ser (c.442C>T) is classified Uncertain significance in CSF3R (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.0982); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with CSF3R p.Pro148Ser (c.442C>T)?

CSF3R p.Pro148Ser (c.442C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CSF3R p.Pro148Ser (c.442C>T) in the general population?

CSF3R p.Pro148Ser (c.442C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CSF3R p.Pro148Ser (c.442C>T)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

CSF3R p.Pro148Ser

c.442C>T · rs145989033 · VCV2235119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.40	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 6.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 3.4e-07 · regional, not allelic
Overall
CADD	23.2	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 6.84e-05%

Overall 6.84e-05% 1/1,461,892 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.Pro148Ser
Coding: c.442C>T
MANE Select: NM_000760
dbSNP: rs145989033
Type: single nucleotide variant
Location: chr1:36473807 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB
Residue 148: the fibronectin type-iii 1 domain

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.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
CSF3R p.Ile35Val 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-pro148ser (accessed [today's date]).

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