Is CSF2RB p.Pro89= (c.267C>T) pathogenic?

CSF2RB p.Pro89= (c.267C>T) is classified Likely benign in CSF2RB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). Very rare (popmax 0.01%, amr).

How common is CSF2RB p.Pro89= (c.267C>T) in the general population?

CSF2RB p.Pro89= (c.267C>T) is very rare (popmax 0.01%, amr) (gnomAD).

CSF2RB p.Pro89=

c.267C>T · rs186958325 · VCV1559404

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -3.4
Overall
CADD	0.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,030 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,614,246 alleles · very rare exomes 4/1,461,890 · genomes 2/152,356 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CSF2RB
Protein: p.Pro89=
Coding: c.267C>T
MANE Select: NM_000395
dbSNP: rs186958325
Type: single nucleotide variant
Location: chr22:36926053 (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 89: a β-strand

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

Similar variants

CSF2RB p.Pro89His Uncertain significance ★ ⚠ 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-pro89 (accessed [today's date]).

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