Is CSF1R p.Ser55fs (c.161dup) pathogenic?

CSF1R p.Ser55fs (c.161dup) is classified Pathogenic in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 0.000169%, nfe).

How common is CSF1R p.Ser55fs (c.161dup) in the general population?

CSF1R p.Ser55fs (c.161dup) is very rare (popmax 0.000169%, nfe) (gnomAD).

CSF1R p.Ser55fs

c.161dup · rs753211296 · VCV1356688

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -4.4, phastCons 0.006

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,004 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,120 alleles · very rare exomes 2/1,461,890 · genomes 0/152,230 · joint denominator

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: CSF1R
Protein: p.Ser55fs
Coding: c.161dup
MANE Select: NM_001288705
dbSNP: rs753211296
Type: Duplication
Location: chr5:150080912 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 55: the ig-like c2-type 1 domain; a turn

Full CSF1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF1R p.Gly934_Ser935insGlyGly Uncertain significance ★★ same type
CSF1R p.Gly936_Ser938dup Uncertain significance ★★ same type
CSF1R p.Phe971fs Uncertain significance ★★ same type
CSF1R p.Ala681fs Likely pathogenic ★ same type
CSF1R p.Glu24fs Likely pathogenic ★ same type
CSF1R p.Ser686fs Pathogenic ★ same type
CSF1R c.2442+2dup Conflicting classifications of pathogenicity ★ ⚠ same type
CSF1R p.Gly936_Ser937insGly 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/csf1r-p-ser55fs (accessed [today's date]).

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