Is CSF3R p.Trp375Cys (c.1125G>T) pathogenic?

CSF3R p.Trp375Cys (c.1125G>T) is classified Uncertain significance in CSF3R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: ambiguous (0.5401); Absent from gnomAD v4.1.

How common is CSF3R p.Trp375Cys (c.1125G>T) in the general population?

CSF3R p.Trp375Cys (c.1125G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF3R p.Trp375Cys (c.1125G>T)?

AlphaMissense predicts ambiguous (score 0.5401) — an in-silico prediction, not a clinical call.

CSF3R p.Trp375Cys

c.1125G>T · rs2124119110 · VCV1695735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5401 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5401	ambiguous
REVEL	0.222	benign-leaning
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.46	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.8	GERP 1.6, phastCons 0.98
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 3.4e-07 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSF3R
Protein: p.Trp375Cys
Coding: c.1125G>T
MANE Select: NM_000760
dbSNP: rs2124119110
Type: single nucleotide variant
Location: chr1:36471593 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB
Residue 375: the fibronectin type-iii 3 domain

Full CSF3R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF3R c.1072-1G>A Pathogenic/Likely pathogenic ★★ same type
CSF3R c.843+2T>C Pathogenic/Likely pathogenic ★★ same type
CSF3R c.998-2A>T Likely pathogenic ★★ same type
CSF3R p.Arg308Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
CSF3R p.Arg440Ter Pathogenic ★★ same type
CSF3R p.Gln114Ter Pathogenic/Likely pathogenic ★★ same type
CSF3R p.Thr618Ile Pathogenic/Likely pathogenic ★★ same type
CSF3R p.Trp547Ter Pathogenic/Likely pathogenic ★★ same type

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-trp375cys (accessed [today's date]).

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