GPC4 p.Phe221=
c.663C>T · VCV4952941
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0035%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.92 | GERP -2.1, phastCons 0.98 |
| Overall | ||
| CADD | 5.484 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0035%
African / African-American · 2/57,152 alleles
Filtering AF
0.00058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000217%
Overall
0.000331%
4/1,209,203 alleles · very rare
exomes 3/1,097,345 · genomes 1/111,858 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0035% | 28,576 |
| South Asian | 0.00177% | 56,555 |
| European (non-Finnish) | 0.000112% | 894,927 |
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
- GPC4
- Protein
- p.Phe221=
- Coding
- c.663C>T
- MANE Select
- NM_001448
- Type
- single nucleotide variant
- Location
- chrX:133324193 (GRCh38)
- Structure
- AlphaFold pLDDT 83.68
Similar variants
- GPC4 p.Gln506Ter Pathogenic ★★ same type
- GPC4 p.Ala217Val Uncertain significance ★★ ⚠ same type
- GPC4 p.Arg219His Uncertain significance ★★ ⚠ same type
- GPC4 p.Asn514Ser Uncertain significance ★★ ⚠ same type
- GPC4 p.Asn92Ser Uncertain significance ★★ ⚠ same type
- GPC4 p.Lys26Glu Uncertain significance ★★ ⚠ same type
- GPC4 p.Pro343Leu Uncertain significance ★★ ⚠ same type
- GPC4 c.160+96A>G 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/gpc4-p-phe221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown