Is CFP p.Arg405Ser (c.1213C>A) pathogenic?

CFP p.Arg405Ser (c.1213C>A) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely pathogenic (0.9264); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFP p.Arg405Ser (c.1213C>A)?

CFP p.Arg405Ser (c.1213C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFP p.Arg405Ser (c.1213C>A) in the general population?

CFP p.Arg405Ser (c.1213C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFP p.Arg405Ser (c.1213C>A)?

AlphaMissense predicts likely pathogenic (score 0.9264) — an in-silico prediction, not a clinical call.

CFP p.Arg405Ser

c.1213C>A · VCV4614292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9264 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,178,564)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9264	likely pathogenic · top 5% in CFP
REVEL	0.597	indeterminate
SaProt	LLR -13.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,178,564). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFP
Protein: p.Arg405Ser
Coding: c.1213C>A
MANE Select: NM_001145252
Type: single nucleotide variant
Location: chrX:47626089 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 405: a β-strand; a disulfide bond; the tsp type-1 6 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFP p.Arg405His Uncertain significance ★ ⚠ same residue
CFP p.Arg405Pro Uncertain significance ★ ⚠ same residue
CFP p.Ala402Gly Uncertain significance ★★ ⚠ same condition
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CFP p.Arg438Trp Uncertain significance ★★ ⚠ same condition
CFP p.Asn307Ser Uncertain significance ★★ ⚠ same condition
CFP p.Glu215Lys Uncertain significance ★★ ⚠ same condition
CFP p.Gly200Asp 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-arg405ser (accessed [today's date]).

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