RETREG1 p.Asp381=
c.1143C>T · rs1738478450 · VCV1565068
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 | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.14 | GERP -1.5 |
| Overall | ||
| CADD | 1.436 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,918 alleles
Overall
6.2e-05%
1/1,613,914 alleles · very rare
exomes 1/1,461,688 · genomes 0/152,226 · 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
- RETREG1
- Protein
- p.Asp381=
- Coding
- c.1143C>T
- MANE Select
- NM_001034850
- dbSNP
- rs1738478450
- Type
- single nucleotide variant
- Location
- chr5:16475092 (GRCh38)
- Gene constraint
- LOEUF 0.843 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 59.87 · 2 PDB
- Residue 381
- the 'disordered' region
Similar variants
- RETREG1 p.Gln145Ter Pathogenic ★★ same type
- RETREG1 p.Ser309Ter Pathogenic ★★ same type
- RETREG1 c.808+6T>C Uncertain significance ★★ same type
- RETREG1 c.*1035T>C Uncertain significance ★★ same type
- RETREG1 p.Arg148Thr Uncertain significance ★★ ⚠ same type
- RETREG1 p.Arg266Cys Uncertain significance ★★ ⚠ same type
- RETREG1 p.Arg266His Uncertain significance ★★ ⚠ same type
- RETREG1 p.Arg268Thr 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/retreg1-p-asp381 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown