Is CSF3 p.Pro204Leu (c.611C>T) pathogenic?

CSF3 p.Pro204Leu (c.611C>T) is classified Uncertain significance in CSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.1954); Very rare (popmax 8.62e-05%, nfe).

How common is CSF3 p.Pro204Leu (c.611C>T) in the general population?

CSF3 p.Pro204Leu (c.611C>T) is very rare (popmax 8.62e-05%, nfe) (gnomAD).

What do computational predictors say about CSF3 p.Pro204Leu (c.611C>T)?

AlphaMissense predicts likely benign (score 0.1954) — an in-silico prediction, not a clinical call.

CSF3 p.Pro204Leu

c.611C>T · VCV3497554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1954 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.62e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1954	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.4, phastCons 0.94
Regional constraint	o/e 0.82	unconstrained · MANE · 1,481 bp · p 0.0041 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P207L vs ClinVar P204L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.62e-05% European (non-Finnish) · 1/1,160,750 alleles

Overall 7.03e-05% 1/1,422,984 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: CSF3
Protein: p.Pro204Leu
Coding: c.611C>T
MANE Select: NM_172219
Type: single nucleotide variant
Location: chr17:40016955 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.67 · 7 PDB
Residue 204: a turn

Full CSF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF3 p.Ala171Thr Benign ★★ same type
CSF3 p.Leu154Met Benign ★★ ⚠ same type
CSF3 p.Pro168= Benign ★★ same type
CSF3 p.Ala23Thr Uncertain significance ★ ⚠ same type
CSF3 p.Ala59Thr Uncertain significance ★ ⚠ same type
CSF3 p.Ala5Val Uncertain significance ★ ⚠ same type
CSF3 p.Glu123Val Uncertain significance ★ ⚠ same type
CSF3 p.His73Gln Uncertain significance ★ ⚠ 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/csf3-p-pro204leu (accessed [today's date]).

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