IVD p.Leu321=
c.961T>C · rs146011049 · VCV507082
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.018%, nfe)
Conditions
2
Inborn genetic diseases
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 -3.1 | GERP -3.2 |
| Overall | ||
| CADD | 2.035 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.018%
European (non-Finnish) · 212/1,180,000 alleles
Filtering AF
0.016%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.0142%
229/1,614,196 alleles · ultra-rare
exomes 211/1,461,828 · genomes 18/152,368 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.018% | 5,566 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,814 |
| South Asian | 0.00659% | 15,180 |
| African / African-American | 0.00266% | 37,532 |
| Admixed American | 0.00167% | 60,034 |
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.Leu321=
- Coding
- c.961T>C
- MANE Select
- NM_002225
- dbSNP
- rs146011049
- Type
- single nucleotide variant
- Location
- chr15:40416078 (GRCh38)
- Gene constraint
- LOEUF 0.776 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.25 · 5 PDB
- Residue 321
- an α-helix
Similar variants
- IVD c.144+1G>A Likely pathogenic ★★ same condition
- IVD c.144+1G>C Pathogenic ★★ same condition
- IVD c.286+2T>C Pathogenic/Likely pathogenic ★★ same condition
- IVD c.286+5G>T Likely pathogenic ★★ same condition
- IVD c.287-1G>A Pathogenic/Likely pathogenic ★★ same condition
- IVD c.287-2A>G Pathogenic/Likely pathogenic ★★ same condition
- IVD c.456+2T>C Pathogenic ★★ same condition
- IVD c.457-2A>G Pathogenic ★★ 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-leu321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown