GPC6 p.Pro518=
c.1554C>T · rs1030400337 · VCV1674384
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -12 | GERP -4.5 |
| Overall | ||
| CADD | 1.594 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Filtering AF
0.00208%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00183%
Overall
0.00254%
41/1,613,574 alleles · ultra-rare
exomes 41/1,461,248 · genomes 0/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| East Asian | 0.00446% | 22,442 |
| European (non-Finnish) | 0.00288% | 34,690 |
| South Asian | 0.0011% | 91,070 |
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
- GPC6
- Protein
- p.Pro518=
- Coding
- c.1554C>T
- MANE Select
- NM_005708
- dbSNP
- rs1030400337
- Type
- single nucleotide variant
- Location
- chr13:94403103 (GRCh38)
- Gene constraint
- LOEUF 0.384 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.67
Similar variants
- GPC6 p.Arg171Trp Pathogenic/Likely pathogenic ★★ same type
- GPC6 p.Ala232Thr Uncertain significance ★★ same type
- GPC6 p.Ala377Thr Uncertain significance ★★ ⚠ same type
- GPC6 p.Ala519Thr Uncertain significance ★★ ⚠ same type
- GPC6 p.Arg110Gln Uncertain significance ★★ ⚠ same type
- GPC6 p.Arg126Trp Uncertain significance ★★ ⚠ same type
- GPC6 p.Arg363His Uncertain significance ★★ same type
- GPC6 p.Arg383Gln 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/gpc6-p-pro518 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown