Is CSF2RA p.Ser7Arg (c.21C>A) pathogenic?

CSF2RA p.Ser7Arg (c.21C>A) is classified Uncertain significance in CSF2RA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Absent from gnomAD v4.1; Associated with surfactant metabolism dysfunction, pulmonary, 4.

What condition is associated with CSF2RA p.Ser7Arg (c.21C>A)?

CSF2RA p.Ser7Arg (c.21C>A) is associated with surfactant metabolism dysfunction, pulmonary, 4 (ClinVar).

How common is CSF2RA p.Ser7Arg (c.21C>A) in the general population?

CSF2RA p.Ser7Arg (c.21C>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

CSF2RA p.Ser7Arg

c.21C>A · rs2090190168 · VCV948700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,784)

Conditions

surfactant metabolism dysfunction, pulmonary, 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.328	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -1.5
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.2 · regional, not allelic
Overall
CADD	4.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,784). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CSF2RA
Protein: p.Ser7Arg
Coding: c.21C>A
MANE Select: NM_172245
dbSNP: rs2090190168
Type: single nucleotide variant
Location: chrX:1282724 (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 p.Ser7Asn Uncertain significance ★ same residue
CSF2RA p.Ser7= Likely benign ★ same residue
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
CSF2RA p.Gly339Val 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-ser7arg (accessed [today's date]).

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