Is CSF2RB p.Ser709fs (c.2124del) pathogenic?

CSF2RB p.Ser709fs (c.2124del) is classified Conflicting classifications of pathogenicity in CSF2RB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0825%, mid).

How common is CSF2RB p.Ser709fs (c.2124del) in the general population?

CSF2RB p.Ser709fs (c.2124del) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

CSF2RB p.Ser709fs

c.2124del · rs568607741 · VCV402566

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

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	escapes	premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -0.82, phastCons 0.96
Overall
CADD	23.4	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 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.072% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0703%

Overall 0.113% 1,832/1,614,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.25%	44
Remaining individualsnot grpmax-eligible	0.245%	409
Finnishnot grpmax-eligible	0.1%	1,000
Middle Easterngrpmax	0.0825%	1,212
European (non-Finnish)	0.0762%	1,313
Admixed American	0.07%	1,429
African / African-American	0.004%	25,010

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CSF2RB
Protein: p.Ser709fs
Coding: c.2124del
MANE Select: NM_000395
dbSNP: rs568607741
Type: Deletion
Location: chr22:36937931 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.93 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.50 · 10 PDB
Residue 709: the 'disordered' region

Full CSF2RB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF2RB p.Trp152fs Uncertain significance ★★ same type
CSF2RB p.Ala662fs Uncertain significance ★ same type
CSF2RB p.Cys16fs Uncertain significance ★ same type
CSF2RB p.Cys745fs Uncertain significance ★ same type
CSF2RB p.Gln194fs Uncertain significance ★ same type
CSF2RB p.Gln660fs Uncertain significance ★ same type
CSF2RB p.Gln856fs Uncertain significance ★ same type
CSF2RB p.Glu627fs 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/csf2rb-p-ser709fs (accessed [today's date]).

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