Is CSF1 p.Glu292= (c.876G>A) pathogenic?

CSF1 p.Glu292= (c.876G>A) is classified Benign in CSF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-05). Common (popmax 9.58%, afr) — too common for a highly-penetrant pathogenic allele.

CSF1 p.Glu292=

Q: How common is CSF1 p.Glu292= (c.876G>A) in the general population?

CSF1 p.Glu292= (c.876G>A) is common (popmax 9.58%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.876G>A · rs12721513 · VCV775573

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.58%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.026	GERP -3, phastCons 0.13
Overall
CADD	0.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.58% African / African-American · 7,185/75,010 alleles

Filtering AF 9.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.32%

Overall 0.565% 9,117/1,614,120 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.58%	10
Middle Eastern	0.973%	103
Admixed American	0.911%	110
Remaining individualsnot grpmax-eligible	0.806%	124
European (non-Finnish)	0.0671%	1,490
South Asian	0.0274%	3,644
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
Finnishnot grpmax-eligible	0.00156%	64,042

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.Glu292=
Coding: c.876G>A
MANE Select: NM_000757
dbSNP: rs12721513
Type: single nucleotide variant
Location: chr1:109923497 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.62 · 8 PDB
Residue 292: 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.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
CSF1 p.Arg449Trp 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-glu292 (accessed [today's date]).

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