Is CSF2RB p.Arg415Ser (c.1245G>C) pathogenic?

CSF2RB p.Arg415Ser (c.1245G>C) is classified Uncertain significance in CSF2RB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-19). AlphaMissense: likely pathogenic (0.6755); Absent from gnomAD v4.1.

How common is CSF2RB p.Arg415Ser (c.1245G>C) in the general population?

CSF2RB p.Arg415Ser (c.1245G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF2RB p.Arg415Ser (c.1245G>C)?

AlphaMissense predicts likely pathogenic (score 0.6755) — an in-silico prediction, not a clinical call.

CSF2RB p.Arg415Ser

c.1245G>C · VCV3659390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6755	likely pathogenic · top 10% in CSF2RB
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.83, phastCons 0.037
Regional constraint	o/e 0.85	unconstrained · MANE · 14 kb · p 0.00014 · regional, not allelic
Overall
CADD	16.21	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.Arg415Ser
Coding: c.1245G>C
MANE Select: NM_000395
Type: single nucleotide variant
Location: chr22:36933924 (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 415: the fibronectin type-iii 2 domain; a β-strand

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

Similar variants

CSF2RB p.Arg415= Likely benign ★ same residue
CSF2RB p.Ala185Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala255Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala314Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala314Val Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala394Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala455Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala576Thr Uncertain significance ★★ ⚠ same type

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-arg415ser (accessed [today's date]).

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