Is CSF2RB p.Pro737Ala (c.2209C>G) pathogenic?

CSF2RB p.Pro737Ala (c.2209C>G) is classified Uncertain significance in CSF2RB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0768); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CSF2RB p.Pro737Ala (c.2209C>G)?

CSF2RB p.Pro737Ala (c.2209C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CSF2RB p.Pro737Ala (c.2209C>G) in the general population?

CSF2RB p.Pro737Ala (c.2209C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF2RB p.Pro737Ala (c.2209C>G)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

CSF2RB p.Pro737Ala

c.2209C>G · rs760821596 · VCV1715271

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -6.40	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 -2.3	GERP -3.2
Regional constraint	o/e 1.07	unconstrained · MANE · 1,937 bp · p 0.11 · regional, not allelic
Overall
CADD	2.929	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.Pro737Ala
Coding: c.2209C>G
MANE Select: NM_000395
dbSNP: rs760821596
Type: single nucleotide variant
Location: chr22:36938017 (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 737: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSF2RB p.Pro737Leu Uncertain significance ★★ ⚠ same residue
CSF2RB p.Ala255Thr Uncertain significance ★★ ⚠ same condition
CSF2RB p.Ala314Thr Uncertain significance ★★ ⚠ same condition
CSF2RB p.Ala314Val Uncertain significance ★★ ⚠ same condition
CSF2RB p.Ala576Thr Uncertain significance ★★ ⚠ same condition
CSF2RB p.Ala662Thr Uncertain significance ★★ ⚠ same condition
CSF2RB p.Arg122Trp Uncertain significance ★★ ⚠ same condition
CSF2RB p.Arg225Cys 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-pro737ala (accessed [today's date]).

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