PROC c.*78del
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.017%, mid)
Conditions
1
PROC-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.17 | GERP -0.49 |
| Non-coding constraint | Z 2.63 | 1 kb window · o/e 0.75 · regional · uncalibrated |
| Overall | ||
| CADD | 2.041 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.017%
Middle Eastern · 1/5,896 alleles
Filtering AF
0.0011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000512%
Overall
0.00112%
17/1,511,784 alleles · ultra-rare
exomes 16/1,359,576 · genomes 1/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.017% | 5,896 |
| African / African-American | 0.00413% | 24,239 |
| European (non-Finnish) | 0.00119% | 83,924 |
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
- PROC
- Coding
- c.*78del
- MANE Select
- NM_000312
- dbSNP
- rs997589614
- Type
- Deletion
- Location
- chr2:127429024 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.35 · 12 PDB
Disease context
PROC-related disorder
Similar variants
- PROC p.Arg220Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PROC p.Arg328Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PROC p.Glu62Ala Pathogenic/Likely pathogenic ★★ same condition
- PROC p.Gly433Asp Likely pathogenic ★★ same condition
- PROC p.His149fs Pathogenic ★★ same condition
- PROC p.Thr340Met Pathogenic ★★ ⚠ same condition
- PROC p.Arg129His Uncertain significance ★★ ⚠ same condition
- PROC c.679-2A>G Likely 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/proc-c-star-78del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown