CFP p.Ser221=
c.663C>T · rs367635632 · VCV775781
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.666%, mid)
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 1.2 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 5.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.666%
Middle Eastern · 29/4,353 alleles
Filtering AF
0.477%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.412%
Overall
0.0203%
246/1,210,065 alleles · rare
exomes 218/1,097,138 · genomes 28/112,927 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.666% | 150 |
| South Asian | 0.0935% | 1,070 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0681% | 1,468 |
| Admixed American | 0.0348% | 2,872 |
| Remaining individualsnot grpmax-eligible | 0.0315% | 3,171 |
| European (non-Finnish) | 0.0125% | 7,989 |
| African / African-American | 0.0104% | 9,587 |
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.Ser221=
- Coding
- c.663C>T
- MANE Select
- NM_001145252
- dbSNP
- rs367635632
- Type
- single nucleotide variant
- Location
- chrX:47627244 (GRCh38)
- Structure
- AlphaFold pLDDT 83.75 · 14 PDB
- Residue 221
- the tsp type-1 3 domain; the 'disordered' region; a β-strand
Similar variants
- 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
- CFP p.Asn307Ser 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-ser221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown