Is CFP p.Trp321Gly (c.961T>G) pathogenic?

CFP p.Trp321Gly (c.961T>G) is classified Pathogenic in CFP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-29). AlphaMissense: likely pathogenic (0.7513); Very rare (popmax 0.00296%, eas).

How common is CFP p.Trp321Gly (c.961T>G) in the general population?

CFP p.Trp321Gly (c.961T>G) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about CFP p.Trp321Gly (c.961T>G)?

AlphaMissense predicts likely pathogenic (score 0.7513) — an in-silico prediction, not a clinical call.

CFP p.Trp321Gly

c.961T>G · rs1603083173 · VCV871201

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7513	likely pathogenic ✓ concordant with ClinVar
REVEL	0.571	indeterminate
SaProt	LLR -13.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	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	24.0	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 0.00296% East Asian · 1/33,833 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000638% 7/1,098,026 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,833
Remaining individualsnot grpmax-eligible	0.0021%	47,620
European (non-Finnish)	0.000558%	179,070

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.Trp321Gly
Coding: c.961T>G
MANE Select: NM_001145252
dbSNP: rs1603083173
Type: single nucleotide variant
Location: chrX:47626499 (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.Trp321Ter Pathogenic ★ same residue
CFP p.Trp321Leu Uncertain significance ★ ⚠ same residue
CFP p.Trp321del Uncertain significance ★ same residue
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-trp321gly (accessed [today's date]).

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