PROC p.Gln395Ter
c.1183C>T · VCV4882008
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.20 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.013 | GERP -3.2 |
| Overall | ||
| CADD | 24.6 | 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
- PROC
- Protein
- p.Gln395Ter
- Coding
- c.1183C>T
- MANE Select
- NM_000312
- Type
- single nucleotide variant
- Location
- chr2:127428743 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.35 · 12 PDB
- Residue 395
- the peptidase s1 domain
Similar variants
- PROC p.Ala178Pro Likely pathogenic ★★ ⚠ same type
- PROC p.Ala309Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg199Ter Pathogenic ★★ same type
- PROC p.Arg211Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg211Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg220Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg220Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- PROC p.Arg271Trp Pathogenic/Likely pathogenic ★★ 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/proc-p-gln395ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown