Is CSF1 p.Trp15Arg (c.43T>A) pathogenic?

CSF1 p.Trp15Arg (c.43T>A) is classified Uncertain significance in CSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.7203); Very rare (popmax 0.00452%, sas).

How common is CSF1 p.Trp15Arg (c.43T>A) in the general population?

CSF1 p.Trp15Arg (c.43T>A) is very rare (popmax 0.00452%, sas) (gnomAD).

What do computational predictors say about CSF1 p.Trp15Arg (c.43T>A)?

AlphaMissense predicts likely pathogenic (score 0.7203) — an in-silico prediction, not a clinical call.

CSF1 p.Trp15Arg

c.43T>A · VCV4234798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7203 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00452%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7203	likely pathogenic · top 7% in CSF1
REVEL	0.263	benign-leaning
SaProt	LLR -5.78	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 3,303 bp · p 0.27 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 0.00452% South Asian · 4/88,476 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000911%

Overall 0.000312% 5/1,603,564 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00452%	22,119
Remaining individualsnot grpmax-eligible	0.00161%	62,186

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.Trp15Arg
Coding: c.43T>A
MANE Select: NM_000757
Type: single nucleotide variant
Location: chr1:109914262 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.62 · 8 PDB

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-trp15arg (accessed [today's date]).

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