Is CSF2RB p.Ala749Pro (c.2245G>C) pathogenic?

CSF2RB p.Ala749Pro (c.2245G>C) is classified Uncertain significance in CSF2RB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-17). AlphaMissense: likely benign (0.0774); Absent from gnomAD v4.1; Associated with surfactant metabolism dysfunction, pulmonary, 5.

What condition is associated with CSF2RB p.Ala749Pro (c.2245G>C)?

CSF2RB p.Ala749Pro (c.2245G>C) is associated with surfactant metabolism dysfunction, pulmonary, 5 (ClinVar).

How common is CSF2RB p.Ala749Pro (c.2245G>C) in the general population?

CSF2RB p.Ala749Pro (c.2245G>C) 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.

What do computational predictors say about CSF2RB p.Ala749Pro (c.2245G>C)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

CSF2RB p.Ala749Pro

c.2245G>C · rs2518010646 · VCV2440578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

surfactant metabolism dysfunction, pulmonary, 5

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -3.2
Regional constraint	o/e 1.07	unconstrained · MANE · 1,937 bp · p 0.11 · regional, not allelic
Overall
CADD	7.633	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSF2RB
Protein: p.Ala749Pro
Coding: c.2245G>C
MANE Select: NM_000395
dbSNP: rs2518010646
Type: single nucleotide variant
Location: chr22:36938053 (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 749: 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.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
CSF2RB p.Thr50Ile Uncertain significance ★★ ⚠ same condition
CSF2RB p.Arg215His Benign/Likely benign ★★ same condition
CSF2RB p.Gly423Arg 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-ala749pro (accessed [today's date]).

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