Is CSF2 p.Phe136Leu (c.406T>C) pathogenic?

CSF2 p.Phe136Leu (c.406T>C) is classified Uncertain significance in CSF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely pathogenic (0.5706); Absent from gnomAD v4.1.

How common is CSF2 p.Phe136Leu (c.406T>C) in the general population?

CSF2 p.Phe136Leu (c.406T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSF2 p.Phe136Leu (c.406T>C)?

AlphaMissense predicts likely pathogenic (score 0.5706) — an in-silico prediction, not a clinical call.

CSF2 p.Phe136Leu

c.406T>C · VCV4007319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5706 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5706	likely pathogenic
REVEL	0.034	moderately benign-leaning
SaProt	LLR -4.65	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.039	GERP -5.2
Regional constraint	o/e 0.78	unconstrained · MANE · 2,025 bp · p 0.0039 · regional, not allelic
Overall
CADD	4.433	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSF2
Protein: p.Phe136Leu
Coding: c.406T>C
MANE Select: NM_000758
Type: single nucleotide variant
Location: chr5:132075823 (GRCh38)
Gene constraint: LOEUF 0.619 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 88.30 · 11 PDB
Residue 136: a disulfide bond

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

Similar variants

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
CSF2 p.Met53Thr 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-phe136leu (accessed [today's date]).

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