IVD p.Pro389Arg
c.1166C>G · VCV3350446
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.674%, sas)
Conditions
1
IVD-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.25 | GERP 0.004 |
| Overall | ||
| CADD | 3.652 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.674%
South Asian · 504/74,740 alleles
Filtering AF
0.626%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.606%
Overall
0.34%
4,212/1,237,598 alleles · rare
exomes 3,865/1,085,284 · genomes 347/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.674% | 148 |
| Middle Eastern | 0.422% | 237 |
| European (non-Finnish) | 0.354% | 283 |
| Remaining individualsnot grpmax-eligible | 0.336% | 298 |
| Ashkenazi Jewishnot grpmax-eligible | 0.146% | 687 |
| Admixed American | 0.143% | 700 |
| Finnishnot grpmax-eligible | 0.101% | 991 |
| African / African-American | 0.0979% | 1,021 |
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
- IVD
- Protein
- p.Pro389Arg
- Coding
- c.1166C>G
- MANE Select
- NM_002225 · reported on NM_001354601
- Type
- single nucleotide variant
- Location
- chr15:40435444 (GRCh38)
- Gene constraint
- LOEUF 0.776 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.25 · 5 PDB
Disease context
IVD-related disorder
Similar variants
- IVD p.Pro389Leu Uncertain significance ★ ⚠ same residue
- IVD p.Pro389Thr Uncertain significance ★ ⚠ same residue
- IVD p.Pro389= Likely benign ★ same residue
- IVD p.Ala311Val Pathogenic ★★ ⚠ same condition
- IVD p.Arg50Cys Pathogenic/Likely pathogenic ★★ same condition
- IVD p.Gly120Arg Pathogenic/Likely pathogenic ★★ same condition
- IVD p.Thr236Ile Likely pathogenic ★★ ⚠ same condition
- IVD c.550+1G>A Conflicting classifications of pathogenicity ★ 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/ivd-p-pro389arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown