Is CFP p.Gly41Ser (c.121G>A) pathogenic?

CFP p.Gly41Ser (c.121G>A) is classified Benign/Likely benign in CFP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0972); Ultra-rare (popmax 0.0335%, nfe); Associated with properdin deficiency, X-linked.

What condition is associated with CFP p.Gly41Ser (c.121G>A)?

CFP p.Gly41Ser (c.121G>A) is associated with properdin deficiency, X-linked (ClinVar).

How common is CFP p.Gly41Ser (c.121G>A) in the general population?

CFP p.Gly41Ser (c.121G>A) is ultra-rare (popmax 0.0335%, nfe) (gnomAD).

How is Properdin deficiency inherited?

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

What do computational predictors say about CFP p.Gly41Ser (c.121G>A)?

AlphaMissense predicts likely benign (score 0.0972) — an in-silico prediction, not a clinical call.

CFP p.Gly41Ser

c.121G>A · rs374687577 · VCV1166179

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0972 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

properdin deficiency, X-linked

Computational evidence

Protein change
AlphaMissense	0.0972	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -8.86	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 1.3	GERP -0.58, phastCons 0.77
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	15.31	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 0.0335% European (non-Finnish) · 279/831,736 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.029%

Overall 0.0285% 314/1,101,717 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0335%	2,981
Remaining individualsnot grpmax-eligible	0.0335%	2,983
East Asian	0.0307%	3,257
Finnishnot grpmax-eligible	0.013%	7,699
South Asian	0.0116%	8,626
African / African-American	0.0038%	26,314

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.Gly41Ser
Coding: c.121G>A
MANE Select: NM_001145252
dbSNP: rs374687577
Type: single nucleotide variant
Location: chrX:47629630 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 41: the tsp type-1 0 domain; a disulfide bond

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 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
CFP p.Pro239Leu Conflicting classifications of pathogenicity ★ ⚠ 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-gly41ser (accessed [today's date]).

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