Is CFP p.Ser206Ter (c.617C>G) pathogenic?

CFP p.Ser206Ter (c.617C>G) is classified Pathogenic in CFP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-07-01). Very rare (popmax 0.000224%, nfe); Associated with properdin deficiency, X-linked.

What condition is associated with CFP p.Ser206Ter (c.617C>G)?

CFP p.Ser206Ter (c.617C>G) is associated with properdin deficiency, X-linked (ClinVar).

How common is CFP p.Ser206Ter (c.617C>G) in the general population?

CFP p.Ser206Ter (c.617C>G) is very rare (popmax 0.000224%, nfe) (gnomAD).

How is Properdin deficiency inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CFP p.Ser206Ter

c.617C>G · rs132630260 · VCV11184

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Conditions

properdin deficiency, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.56, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000224% European (non-Finnish) · 2/892,076 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000183% 2/1,092,119 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: CFP
Protein: p.Ser206Ter
Coding: c.617C>G
MANE Select: NM_001145252
dbSNP: rs132630260
Type: single nucleotide variant
Location: chrX:47627290 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 206: a disulfide bond; the tsp type-1 3 domain

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

Disease context

properdin deficiency, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Properdin deficiency (Orphanet):

Inheritance: X-linked recessive

Similar variants

CFP p.Arg157Gln Uncertain significance ★★ ⚠ same condition
CFP p.Glu215Lys Uncertain significance ★★ ⚠ same condition
CFP p.Gly41Ser Benign/Likely benign ★★ same condition
CFP c.767-2A>T Likely pathogenic ★ same condition
CFP p.Arg161Ter Pathogenic ★ same condition
CFP p.Ala242Ser Uncertain significance ★ ⚠ same condition
CFP p.Arg159His Conflicting classifications of pathogenicity ★ ⚠ same condition
CFP p.Pro134Ser Uncertain significance ★ ⚠ same condition

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/cfp-p-ser206ter (accessed [today's date]).

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