PROC c.262+5G>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00172%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +5 | donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.94 | donor loss · deltas |
| Pangolin | Δ0.69 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | phastCons 1 |
| Overall | ||
| CADD | 23.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00172%
Admixed American · 1/58,246 alleles
Overall
6.26e-05%
1/1,598,688 alleles · very rare
exomes 1/1,446,318 · genomes 0/152,370 · joint denominator
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.262+5G>C
- MANE Select
- NM_000312
- Type
- single nucleotide variant
- Location
- chr2:127422946 (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-262-plus-5g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown