Is CSF2RA p.Arg161del (c.477_479del) pathogenic?

CSF2RA p.Arg161del (c.477479del) is classified Uncertain significance in CSF2RA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). Very rare (popmax 8.48e-05%, nfe); Associated with surfactant metabolism dysfunction, pulmonary, 4.

What condition is associated with CSF2RA p.Arg161del (c.477_479del)?

CSF2RA p.Arg161del (c.477_479del) is associated with surfactant metabolism dysfunction, pulmonary, 4 (ClinVar).

How common is CSF2RA p.Arg161del (c.477_479del) in the general population?

CSF2RA p.Arg161del (c.477_479del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

CSF2RA p.Arg161del

c.477_479del · rs1325137344 · VCV1441935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

surfactant metabolism dysfunction, pulmonary, 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.15	GERP 1.3, phastCons 0.036
Overall
CADD	1.456	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,986 alleles

Overall 0.000658% 1/151,988 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.Arg161del
Coding: c.477_479del
MANE Select: NM_172245
dbSNP: rs1325137344
Type: Deletion
Location: chrX:1290338 (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 p.Leu74fs Pathogenic ★ same condition
CSF2RA c.220-3del 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-arg161del (accessed [today's date]).

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