Is CFP p.Trp321del (c.961_963del) pathogenic?

CFP p.Trp321del (c.961963del) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). Very rare (popmax 0.00175%, sas).

How common is CFP p.Trp321del (c.961_963del) in the general population?

CFP p.Trp321del (c.961_963del) is very rare (popmax 0.00175%, sas) (gnomAD).

CFP p.Trp321del

c.961_963del · VCV4721737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00175%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -1.7, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% South Asian · 1/56,982 alleles

Overall 8.25e-05% 1/1,211,676 alleles · very rare exomes 1/1,098,060 · genomes 0/113,616 · joint denominator

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.Trp321del
Coding: c.961_963del
MANE Select: NM_001145252
Type: Deletion
Location: chrX:47626497 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 321: an α-helix; the tsp type-1 5 domain

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

Similar variants

CFP p.Trp321Gly Pathogenic ★★ same residue
CFP p.Trp321Ter Pathogenic ★ same residue
CFP p.Trp321Leu Uncertain significance ★ ⚠ same residue
CFP p.Trp388fs Uncertain significance ★ same type
CFP c.1132+15_1132+16del Likely benign ★ same type
CFP c.1245-11del Likely benign ★ same type
CFP c.574+18del Likely benign ★ 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-trp321del (accessed [today's date]).

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