Is CSF2RB p.Ser841Phe (c.2522C>T) pathogenic?

CSF2RB p.Ser841Phe (c.2522C>T) is classified Uncertain significance in CSF2RB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-06). AlphaMissense: likely benign (0.1053); Very rare (popmax 0.00636%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CSF2RB p.Ser841Phe (c.2522C>T)?

CSF2RB p.Ser841Phe (c.2522C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CSF2RB p.Ser841Phe (c.2522C>T) in the general population?

CSF2RB p.Ser841Phe (c.2522C>T) is very rare (popmax 0.00636%, nfe) (gnomAD).

What do computational predictors say about CSF2RB p.Ser841Phe (c.2522C>T)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

CSF2RB p.Ser841Phe

c.2522C>T · rs376607600 · VCV2409576

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -8.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP -1.9, phastCons 0.006
Regional constraint	o/e 1.07	unconstrained · MANE · 1,937 bp · p 0.11 · regional, not allelic
Overall
CADD	19.34	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

Grpmax group 0.00636% European (non-Finnish) · 75/1,180,038 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00502% 81/1,614,086 alleles · very rare exomes 71/1,461,874 · genomes 10/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,734
Admixed American	0.00333%	30,006
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	74,924
South Asian	0.0011%	91,094

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.Ser841Phe
Coding: c.2522C>T
MANE Select: NM_000395
dbSNP: rs376607600
Type: single nucleotide variant
Location: chr22:36938330 (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 841: 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-ser841phe (accessed [today's date]).

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