Is CSF3 p.Ser22Gly (c.64A>G) pathogenic?

CSF3 p.Ser22Gly (c.64A>G) is classified Uncertain significance in CSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0749); Very rare (popmax 0.000343%, nfe).

How common is CSF3 p.Ser22Gly (c.64A>G) in the general population?

CSF3 p.Ser22Gly (c.64A>G) is very rare (popmax 0.000343%, nfe) (gnomAD).

What do computational predictors say about CSF3 p.Ser22Gly (c.64A>G)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

CSF3 p.Ser22Gly

c.64A>G · rs755462486 · VCV2530042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000343%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.02	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 1.5	GERP 0.63, phastCons 0.17
Regional constraint	o/e 0.82	unconstrained · MANE · 1,481 bp · p 0.0041 · regional, not allelic
Overall
CADD	14.15	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 0.000343% European (non-Finnish) · 4/1,166,856 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000278% 4/1,438,402 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.Ser22Gly
Coding: c.64A>G
MANE Select: NM_172219
dbSNP: rs755462486
Type: single nucleotide variant
Location: chr17:40015714 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.67 · 7 PDB

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-ser22gly (accessed [today's date]).

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