Is CSF2RB p.Ser355Arg (c.1065C>A) pathogenic?

CSF2RB p.Ser355Arg (c.1065C>A) is classified Uncertain significance in CSF2RB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-25). AlphaMissense: ambiguous (0.4786); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CSF2RB p.Ser355Arg (c.1065C>A)?

CSF2RB p.Ser355Arg (c.1065C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CSF2RB p.Ser355Arg (c.1065C>A) in the general population?

CSF2RB p.Ser355Arg (c.1065C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CSF2RB p.Ser355Arg (c.1065C>A)?

AlphaMissense predicts ambiguous (score 0.4786) — an in-silico prediction, not a clinical call.

CSF2RB p.Ser355Arg

c.1065C>A · rs746796915 · VCV1968178

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4786 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4786	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -7.23	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -1.8
Regional constraint	o/e 0.85	unconstrained · MANE · 14 kb · p 0.00014 · regional, not allelic
Overall
CADD	11.67	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

Grpmax group 0.00167% Admixed American · 1/59,992 alleles

Overall 0.000682% 11/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
Admixed Americangrpmax	0.00167%	59,992
European (non-Finnish)	8.47e-05%	1,180,054

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser355Arg
Coding: c.1065C>A
MANE Select: NM_000395
dbSNP: rs746796915
Type: single nucleotide variant
Location: chr22:36932817 (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 355: the fibronectin type-iii 2 domain; a β-strand

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.Ser355= Likely benign ★ same residue
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

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-ser355arg (accessed [today's date]).

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