Is CSF2RB p.Pro648Leu (c.1943_1944inv) pathogenic?

CSF2RB p.Pro648Leu (c.19431944inv) is classified Uncertain significance in CSF2RB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-22). Associated with surfactant metabolism dysfunction, pulmonary, 5.

What condition is associated with CSF2RB p.Pro648Leu (c.1943_1944inv)?

CSF2RB p.Pro648Leu (c.1943_1944inv) is associated with surfactant metabolism dysfunction, pulmonary, 5 (ClinVar).

How is Hereditary pulmonary alveolar proteinosis inherited?

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

CSF2RB p.Pro648Leu

c.1943_1944inv · VCV1002560

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

Conditions

surfactant metabolism dysfunction, pulmonary, 5

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 -0.89	GERP -1.3
Regional constraint	o/e 1.07	unconstrained · MANE · 1,937 bp · p 0.11 · regional, not allelic

Variant & gene context

Gene: CSF2RB
Protein: p.Pro648Leu
Coding: c.1943_1944inv
MANE Select: NM_000395
Type: Inversion
Location: chr22:36937751 (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 648: the 'disordered' region

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

Disease context

surfactant metabolism dysfunction, pulmonary, 5 — 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

CSF2RB p.Pro648= Benign ★★ same residue
CSF2RB p.Pro648Arg Uncertain significance ★ same residue
CSF2RB p.Pro648Ser Uncertain significance ★ ⚠ same residue
CSF2RB p.Arg211Gln Uncertain significance ★★ ⚠ same condition
CSF2RB p.Arg461Cys Uncertain significance ★★ ⚠ same condition
CSF2RB p.Glu533Lys Uncertain significance ★★ ⚠ same condition
CSF2RB p.Gly845Ser Uncertain significance ★★ ⚠ same condition
CSF2RB p.Thr196Asn 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/csf2rb-p-pro648leu (accessed [today's date]).

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