Is CSF2RB p.Ser181Pro (c.541T>C) pathogenic?

CSF2RB p.Ser181Pro (c.541T>C) is classified Uncertain significance in CSF2RB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.116); Ultra-rare (popmax 0.0248%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CSF2RB p.Ser181Pro (c.541T>C)?

CSF2RB p.Ser181Pro (c.541T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CSF2RB p.Ser181Pro (c.541T>C) in the general population?

CSF2RB p.Ser181Pro (c.541T>C) is ultra-rare (popmax 0.0248%, nfe) (gnomAD).

What do computational predictors say about CSF2RB p.Ser181Pro (c.541T>C)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

CSF2RB p.Ser181Pro

c.541T>C · rs370781346 · VCV1007278

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0248%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -6.91	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 0.091	GERP 0.45, phastCons 0.15
Regional constraint	o/e 0.85	unconstrained · MANE · 14 kb · p 0.00014 · regional, not allelic
Overall
CADD	17.27	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 0.0248% European (non-Finnish) · 293/1,180,016 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0216%

Overall 0.019% 306/1,613,996 alleles · ultra-rare exomes 294/1,461,882 · genomes 12/152,114 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0248%	4,027
Remaining individualsnot grpmax-eligible	0.0144%	6,943
African / African-American	0.00401%	24,963
Finnishnot grpmax-eligible	0.00156%	64,030

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.Ser181Pro
Coding: c.541T>C
MANE Select: NM_000395
dbSNP: rs370781346
Type: single nucleotide variant
Location: chr22:36929551 (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 181: the fibronectin type-iii 1 domain

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-ser181pro (accessed [today's date]).

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