Is CFP p.Arg405Pro (c.1214G>C) pathogenic?

CFP p.Arg405Pro (c.1214G>C) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.9769); Absent from gnomAD v4.1.

How common is CFP p.Arg405Pro (c.1214G>C) in the general population?

CFP p.Arg405Pro (c.1214G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFP p.Arg405Pro (c.1214G>C)?

AlphaMissense predicts likely pathogenic (score 0.9769) — an in-silico prediction, not a clinical call.

CFP p.Arg405Pro

c.1214G>C · VCV4075570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9769 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9769	likely pathogenic · top 1% in CFP
REVEL	0.627	indeterminate
SaProt	LLR -16.33	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.33	donor loss · deltas
Pangolin	Δ0.27	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	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	25.7	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

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: CFP
Protein: p.Arg405Pro
Coding: c.1214G>C
MANE Select: NM_001145252
Type: single nucleotide variant
Location: chrX:47626088 (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

Similar variants

CFP p.Arg405His Uncertain significance ★ ⚠ same residue
CFP p.Arg405Ser Uncertain significance ★ ⚠ same residue
CFP p.Trp321Gly Pathogenic ★★ same type
CFP p.Ala402Gly Uncertain significance ★★ ⚠ same type
CFP p.Arg157Gln Uncertain significance ★★ ⚠ same type
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same type
CFP p.Arg159Cys Uncertain significance ★★ ⚠ same type
CFP p.Arg247Trp 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/cfp-p-arg405pro (accessed [today's date]).

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