Is CSF3R p.Ala530fs (c.1587dup) pathogenic?

CSF3R p.Ala530fs (c.1587dup) is classified Likely pathogenic in CSF3R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). Very rare (popmax 0.000257%, nfe).

How common is CSF3R p.Ala530fs (c.1587dup) in the general population?

CSF3R p.Ala530fs (c.1587dup) is very rare (popmax 0.000257%, nfe) (gnomAD).

CSF3R p.Ala530fs

c.1587dup · rs758886187 · VCV2439595

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.37	GERP -0.53, phastCons 0.027
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000257% European (non-Finnish) · 3/1,167,940 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000189% 3/1,591,030 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: CSF3R
Protein: p.Ala530fs
Coding: c.1587dup
MANE Select: NM_000760
dbSNP: rs758886187
Type: Duplication
Location: chr1:36468210 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 1 PDB
Residue 530: the fibronectin type-iii 5 domain

Full CSF3R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF3R p.Ala530Val Uncertain significance ★ ⚠ same residue
CSF3R p.Arg74fs Pathogenic ★ same type
CSF3R p.Met231fs Pathogenic ★ same type
CSF3R p.Ser238fs Pathogenic ★ same type
CSF3R p.Val406fs Pathogenic ★ same type
CSF3R c.1071+1_1071+5dup Uncertain significance ★ same type
CSF3R c.2041-164_2132dup Uncertain significance ★ same type
CSF3R p.Gln730fs 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/csf3r-p-ala530fs (accessed [today's date]).

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