GPC4 p.Pro240Ser
c.718C>T · VCV4530923
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3543 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3543 | ambiguous |
|---|---|---|
| REVEL | 0.133 | moderately benign-leaning |
| SaProt | LLR -9.58 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.59 | unconstrained · MANE · 34 kb · p 6.9e-12 · regional, not allelic |
| Overall | ||
| CADD | 17.76 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- GPC4
- Protein
- p.Pro240Ser
- Coding
- c.718C>T
- MANE Select
- NM_001448
- Type
- single nucleotide variant
- Location
- chrX:133311417 (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-pro240ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown