GPC4 p.Gln537Ter
c.1609C>T · rs2520389876 · VCV2584833
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
GPC4-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 29.5 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Gln537Ter
- Coding
- c.1609C>T
- MANE Select
- NM_001448
- dbSNP
- rs2520389876
- Type
- single nucleotide variant
- Location
- chrX:133302929 (GRCh38)
- Structure
- AlphaFold pLDDT 83.68
- Residue 537
- a UniProt-annotated variant site (in kpts; increased proteasomal degradation)
Similar variants
- GPC4 p.Gln506Ter Pathogenic ★★ same condition
- GPC4 p.Ala217Val Uncertain significance ★★ ⚠ same condition
- GPC4 p.Arg219His Uncertain significance ★★ ⚠ same condition
- GPC4 c.-20C>T Benign ★★ same condition
- GPC4 p.Ala442Val Benign ★★ same condition
- GPC4 p.Glu391Asp Benign ★★ same condition
- GPC4 p.Arg351Ter Likely pathogenic ★ same condition
- GPC4 p.Glu496Ter Pathogenic ★ same condition
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-gln537ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown