Is CSF2RB p.Ser426= (c.1278C>T) pathogenic?

CSF2RB p.Ser426= (c.1278C>T) is classified Benign in CSF2RB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 23.8%, mid) — too common for a highly-penetrant pathogenic allele.

CSF2RB p.Ser426=

Q: How common is CSF2RB p.Ser426= (c.1278C>T) in the general population?

CSF2RB p.Ser426= (c.1278C>T) is common (popmax 23.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1278C>T · rs1801117 · VCV226545

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 23.8%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	donor loss · deltas
Constraint at this position
Conservation	phyloP -2.8	GERP -2.9
Overall
CADD	4.473	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.8% Middle Eastern · 1,443/6,060 alleles

Filtering AF 23.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.1%

Overall 21.7% 350,079/1,612,486 alleles · common exomes 318,672/1,460,552 · genomes 31,407/151,934 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	24.6%	4
Middle Easterngrpmax	23.8%	4
African / African-American	23.5%	4
South Asian	23.4%	4
European (non-Finnish)	23%	4
Remaining individualsnot grpmax-eligible	22.3%	4
Ashkenazi Jewishnot grpmax-eligible	18.9%	5
Finnishnot grpmax-eligible	14.9%	7
Admixed American	12.3%	8
East Asian	5.09%	20

Amish 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.Ser426=
Coding: c.1278C>T
MANE Select: NM_000395
dbSNP: rs1801117
Type: single nucleotide variant
Location: chr22:36933957 (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 426: the fibronectin type-iii 2 domain; an α-helix

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

Similar variants

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
CSF2RB p.Ala662Thr 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-ser426 (accessed [today's date]).

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