Is CSF2RB p.Leu734Pro (c.2201T>C) pathogenic?

CSF2RB p.Leu734Pro (c.2201T>C) is classified Likely benign in CSF2RB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.0511); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CSF2RB p.Leu734Pro (c.2201T>C)?

CSF2RB p.Leu734Pro (c.2201T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CSF2RB p.Leu734Pro (c.2201T>C) in the general population?

CSF2RB p.Leu734Pro (c.2201T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF2RB p.Leu734Pro (c.2201T>C)?

AlphaMissense predicts likely benign (score 0.0511) — an in-silico prediction, not a clinical call.

CSF2RB p.Leu734Pro

c.2201T>C · VCV3497548

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0511 · 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	0.0511	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -5.19	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 -3	GERP -3
Regional constraint	o/e 1.07	unconstrained · MANE · 1,937 bp · p 0.11 · regional, not allelic
Overall
CADD	0.138	PHRED · no single calibrated threshold — expert panels disagree

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.Leu734Pro
Coding: c.2201T>C
MANE Select: NM_000395
Type: single nucleotide variant
Location: chr22:36938009 (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 734: 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.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
CSF2RB p.Arg225His 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-leu734pro (accessed [today's date]).

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