Is CSF1 p.Ser430Phe (c.1289C>T) pathogenic?

CSF1 p.Ser430Phe (c.1289C>T) is classified Uncertain significance in CSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.0987); Very rare (popmax 0.00891%, eas).

How common is CSF1 p.Ser430Phe (c.1289C>T) in the general population?

CSF1 p.Ser430Phe (c.1289C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CSF1 p.Ser430Phe (c.1289C>T)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CSF1 p.Ser430Phe

c.1289C>T · rs776875416 · VCV2553823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -8.47	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 3.1	GERP 0.62, phastCons 0.068
Regional constraint	o/e 1.00	unconstrained · MANE · 7,862 bp · p 0.92 · regional, not allelic
Overall
CADD	19.07	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 0.00891% East Asian · 4/44,894 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	8.47e-05%	1,179,948

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: CSF1
Protein: p.Ser430Phe
Coding: c.1289C>T
MANE Select: NM_000757
dbSNP: rs776875416
Type: single nucleotide variant
Location: chr1:109923910 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.62 · 8 PDB
Residue 430: the 'disordered' region

Full CSF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF1 p.Ala511= Benign ★★ same type
CSF1 p.Glu292= Benign ★★ same type
CSF1 p.Ala286Asp Uncertain significance ★ ⚠ same type
CSF1 p.Ala3Thr Uncertain significance ★ ⚠ same type
CSF1 p.Ala460Glu Uncertain significance ★ ⚠ same type
CSF1 p.Arg252Trp Uncertain significance ★ ⚠ same type
CSF1 p.Arg374Met Uncertain significance ★ ⚠ same type
CSF1 p.Arg449Gln 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/csf1-p-ser430phe (accessed [today's date]).

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