Is CSF2RB p.Pro696Ser (c.2086C>T) pathogenic?

CSF2RB p.Pro696Ser (c.2086C>T) is classified Benign/Likely benign in CSF2RB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0782); Common (popmax 11.6%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CSF2RB p.Pro696Ser (c.2086C>T)?

AlphaMissense predicts likely benign (score 0.0782) — an in-silico prediction, not a clinical call.

CSF2RB p.Pro696Ser

Q: How common is CSF2RB p.Pro696Ser (c.2086C>T) in the general population?

CSF2RB p.Pro696Ser (c.2086C>T) is common (popmax 11.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2086C>T · rs16997517 · VCV226551

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0782 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0782	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -6.03	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 -0.21	GERP -2.9
Regional constraint	o/e 1.07	unconstrained · MANE · 1,937 bp · p 0.11 · regional, not allelic
Overall
CADD	1.055	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 11.6% African / African-American · 8,723/75,018 alleles

Filtering AF 11.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.3%

Overall 2.54% 40,950/1,614,106 alleles · common exomes 34,058/1,461,856 · genomes 6,892/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.6%	9
Amishnot grpmax-eligible	5.59%	18
South Asian	5.32%	19
Middle Eastern	4.01%	25
Remaining individualsnot grpmax-eligible	2.6%	39
European (non-Finnish)	2%	50
Admixed American	1.88%	53
Ashkenazi Jewishnot grpmax-eligible	1.26%	80
Finnishnot grpmax-eligible	0.537%	186
East Asian	0.0223%	4,488

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.Pro696Ser
Coding: c.2086C>T
MANE Select: NM_000395
dbSNP: rs16997517
Type: single nucleotide variant
Location: chr22:36937894 (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 696: a UniProt-annotated variant site (in); the 'disordered' region

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-pro696ser (accessed [today's date]).

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