Is CSF2RA p.Leu74fs (c.221del) pathogenic?

CSF2RA p.Leu74fs (c.221del) is classified Pathogenic in CSF2RA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). Associated with surfactant metabolism dysfunction, pulmonary, 4.

What condition is associated with CSF2RA p.Leu74fs (c.221del)?

CSF2RA p.Leu74fs (c.221del) is associated with surfactant metabolism dysfunction, pulmonary, 4 (ClinVar).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

CSF2RA p.Leu74fs

c.221del · VCV3689735

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 5 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.32	GERP -0.32, phastCons 0.004

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

Variant & gene context

Gene: CSF2RA
Protein: p.Leu74fs
Coding: c.221del
MANE Select: NM_172245
Type: Deletion
Location: chrX:1288520 (GRCh38)
Structure: AlphaFold pLDDT 82.15 · 2 PDB

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.473+16_473+17del Benign/Likely benign ★★ same condition
CSF2RA p.Arg289fs Pathogenic ★ same condition
CSF2RA p.Asn123fs Pathogenic ★ same condition
CSF2RA p.Leu183fs Pathogenic ★ same condition
CSF2RA c.220-3del Uncertain significance ★ same condition
CSF2RA p.Arg161del Uncertain significance ★ same condition
CSF2RA c.473+14_473+15del Likely benign ★ same condition
CSF2RA p.Arg199Ter Pathogenic ★★ 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-leu74fs (accessed [today's date]).

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