PROC p.Glu154del
c.458AGG[1] · VCV4540670
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00119%, sas)
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 0.47 | phastCons 0.14 |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00119%
South Asian · 1/84,072 alleles
Filtering AF
8.2e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.5e-05%
Overall
0.000323%
5/1,550,222 alleles · very rare
exomes 5/1,397,954 · genomes 0/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00119% | 84,072 |
| European (non-Finnish) | 0.000349% | 286,763 |
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
- Protein
- p.Glu154del
- Coding
- c.458AGG[1]
- MANE Select
- NM_000312
- Type
- Microsatellite
- Location
- chr2:127423330 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.35 · 12 PDB
- Residue 154
- the egf-like 2 domain
Similar variants
- PROC p.Glu154= Likely benign ★★ same residue
- PROC p.Glu154Lys Uncertain significance ★ ⚠ same residue
- PROC p.Cys111fs Pathogenic ★★ same type
- PROC c.-21-5_-21-3del Uncertain significance ★ same type
- PROC p.Gln207_Val208insGluAspGln Uncertain significance ★ same type
- PROC p.Glu62del Uncertain significance ★ same type
- PROC p.Lys193del Conflicting classifications of pathogenicity ★ same type
- PROC p.Lys235del 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/proc-p-glu154del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown