Is CFP p.Arg220= (c.658C>A) pathogenic?

CFP p.Arg220= (c.658C>A) is classified Likely benign in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). Very rare (popmax 0.00134%, nfe).

How common is CFP p.Arg220= (c.658C>A) in the general population?

CFP p.Arg220= (c.658C>A) is very rare (popmax 0.00134%, nfe) (gnomAD).

CFP p.Arg220=

c.658C>A · rs372336803 · VCV1547995

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 1
Overall
CADD	5.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% European (non-Finnish) · 12/894,730 alleles

Filtering AF 0.000715% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000565%

Overall 0.000992% 12/1,209,837 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.Arg220=
Coding: c.658C>A
MANE Select: NM_001145252
dbSNP: rs372336803
Type: single nucleotide variant
Location: chrX:47627249 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 220: a disulfide bond; the tsp type-1 3 domain; the 'disordered' region; a β-strand

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

Similar variants

CFP p.Arg220Gln 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
CFP p.Arg438Trp 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-arg220 (accessed [today's date]).

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