Is CSF2RB p.Val233Ile (c.697G>A) pathogenic?

CSF2RB p.Val233Ile (c.697G>A) is classified Uncertain significance in CSF2RB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.0976); Absent from gnomAD v4.1.

How common is CSF2RB p.Val233Ile (c.697G>A) in the general population?

CSF2RB p.Val233Ile (c.697G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF2RB p.Val233Ile (c.697G>A)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

CSF2RB p.Val233Ile

c.697G>A · rs2517990875 · VCV2827441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -8.04	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 0.8	GERP -2.4, phastCons 0.97
Regional constraint	o/e 0.85	unconstrained · MANE · 14 kb · p 0.00014 · regional, not allelic
Overall
CADD	13.91	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.Val233Ile
Coding: c.697G>A
MANE Select: NM_000395
dbSNP: rs2517990875
Type: single nucleotide variant
Location: chr22:36929786 (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 233: the fibronectin type-iii 1 domain; a β-strand

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

Similar variants

CSF2RB p.Val233Ala Uncertain significance ★ ⚠ same residue
CSF2RB p.Val233= 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

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-val233ile (accessed [today's date]).

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