Is CSF2 p.Ser22Leu (c.65C>T) pathogenic?

CSF2 p.Ser22Leu (c.65C>T) is classified Likely benign in CSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.0672); Very rare (popmax 0.00329%, sas).

How common is CSF2 p.Ser22Leu (c.65C>T) in the general population?

CSF2 p.Ser22Leu (c.65C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CSF2 p.Ser22Leu (c.65C>T)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

CSF2 p.Ser22Leu

c.65C>T · rs777654384 · VCV2379591

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -6.48	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 -2.3	GERP -4.4
Regional constraint	o/e 0.78	unconstrained · MANE · 2,025 bp · p 0.0039 · regional, not allelic
Overall
CADD	0.844	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 0.00329% South Asian · 3/91,074 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00118% 19/1,613,160 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,358
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,054
European (non-Finnish)	0.00119%	84,288

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: CSF2
Protein: p.Ser22Leu
Coding: c.65C>T
MANE Select: NM_000758
dbSNP: rs777654384
Type: single nucleotide variant
Location: chr5:132073888 (GRCh38)
Gene constraint: LOEUF 0.619 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 88.30 · 11 PDB

Full CSF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF2 p.Ser22= Benign ★ same residue
CSF2 p.Thr115Ile Likely benign ★★ same type
CSF2 p.Ala13Thr Uncertain significance ★ ⚠ same type
CSF2 p.Arg21Cys Uncertain significance ★ ⚠ same type
CSF2 p.Arg41His Uncertain significance ★ ⚠ same type
CSF2 p.Arg84Pro Uncertain significance ★ ⚠ same type
CSF2 p.Glu52Asp Uncertain significance ★ ⚠ same type
CSF2 p.Leu127Met 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/csf2-p-ser22leu (accessed [today's date]).

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