Is CX3CL1 p.Pro384Ser (c.1150C>T) pathogenic?

CX3CL1 p.Pro384Ser (c.1150C>T) is classified Uncertain significance in CX3CL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: ambiguous (0.5244); Very rare (popmax 0.00428%, nfe).

How common is CX3CL1 p.Pro384Ser (c.1150C>T) in the general population?

CX3CL1 p.Pro384Ser (c.1150C>T) is very rare (popmax 0.00428%, nfe) (gnomAD).

What do computational predictors say about CX3CL1 p.Pro384Ser (c.1150C>T)?

AlphaMissense predicts ambiguous (score 0.5244) — an in-silico prediction, not a clinical call.

CX3CL1 p.Pro384Ser

c.1150C>T · VCV4008493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5244 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00428%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5244	ambiguous
REVEL	0.181	moderately benign-leaning
SaProt	LLR -6.25	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 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 10 kb · p 0.18 · regional, not allelic
Overall
CADD	23.9	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 0.00428% European (non-Finnish) · 48/1,122,732 alleles

Filtering AF 0.00331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00293%

Overall 0.0032% 48/1,501,518 alleles · very rare

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: CX3CL1
Protein: p.Pro384Ser
Coding: c.1150C>T
MANE Select: NM_002996
Type: single nucleotide variant
Location: chr16:57382988 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 56.75 · 10 PDB

Full CX3CL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CX3CL1 p.Ala62Val Benign ★★ ⚠ same type
CX3CL1 p.Ala85= Benign ★★ same type
CX3CL1 p.Pro241Leu Likely benign ★★ same type
CX3CL1 p.Ser192= Benign ★★ same type
CX3CL1 p.Ala117Val Uncertain significance ★ ⚠ same type
CX3CL1 p.Ala218Thr Uncertain significance ★ ⚠ same type
CX3CL1 p.Ala228Asp Uncertain significance ★ ⚠ same type
CX3CL1 p.Ala235Asp 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/cx3cl1-p-pro384ser (accessed [today's date]).

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