PROC c.70+7C>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +7 | near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.13 | GERP -0.94, phastCons 0.001 |
| Non-coding constraint | Z 3.92 | 1 kb window · o/e 0.62 · regional · uncalibrated |
| Overall | ||
| CADD | 3.335 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,900 alleles
Overall
6.85e-05%
1/1,460,642 alleles · very rare
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.70+7C>G
- MANE Select
- NM_000312
- dbSNP
- rs768681450
- Type
- single nucleotide variant
- Location
- chr2:127420019 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.35 · 12 PDB
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-c-70-plus-7c-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown