Is CSF2RA p.Ser308fs (c.920_921dup) pathogenic?

CSF2RA p.Ser308fs (c.920921dup) is classified Pathogenic in CSF2RA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Very rare (popmax 0.00267%, afr); Associated with surfactant metabolism dysfunction, pulmonary, 4.

What condition is associated with CSF2RA p.Ser308fs (c.920_921dup)?

CSF2RA p.Ser308fs (c.920_921dup) is associated with surfactant metabolism dysfunction, pulmonary, 4 (ClinVar).

How common is CSF2RA p.Ser308fs (c.920_921dup) in the general population?

CSF2RA p.Ser308fs (c.920_921dup) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CSF2RA p.Ser308fs

c.920_921dup · rs1196937077 · VCV1685679

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

surfactant metabolism dysfunction, pulmonary, 4

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 10 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.043	GERP -1.8, phastCons 0.96

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,028 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000137% 2/1,461,650 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: CSF2RA
Protein: p.Ser308fs
Coding: c.920_921dup
MANE Select: NM_172245
dbSNP: rs1196937077
Type: Duplication
Location: chrX:1300599 (GRCh38)
Structure: AlphaFold pLDDT 82.15 · 2 PDB
Residue 308: the fibronectin type-iii domain

Full CSF2RA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

surfactant metabolism dysfunction, pulmonary, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary pulmonary alveolar proteinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

CSF2RA c.774_780+10dup Benign/Likely benign ★★ same condition
CSF2RA p.Leu47fs Pathogenic ★ same condition
CSF2RA p.Val224fs Pathogenic ★ same condition
CSF2RA p.Arg199Ter Pathogenic ★★ same condition
CSF2RA p.Arg217Ter Pathogenic/Likely pathogenic ★★ same condition
CSF2RA p.Gln204Ter Pathogenic ★★ same condition
CSF2RA p.Gln263Ter Pathogenic/Likely pathogenic ★★ same condition
CSF2RA p.Arg354Gln Uncertain significance ★★ same condition

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/csf2ra-p-ser308fs (accessed [today's date]).

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