NIPBL p.Pro464=
c.1392T>A · rs555179389 · VCV199182
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0468%, eas)
Conditions
1
Cornelia de Lange syndrome 1
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 2.2 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 9.371 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0468%
East Asian · 21/44,866 alleles
Filtering AF
0.0313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0263%
Overall
0.00136%
22/1,613,626 alleles · ultra-rare
exomes 19/1,461,438 · genomes 3/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0468% | 2,136 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,498 |
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
- NIPBL
- Protein
- p.Pro464=
- Coding
- c.1392T>A
- MANE Select
- NM_133433
- dbSNP
- rs555179389
- Type
- single nucleotide variant
- Location
- chr5:36976299 (GRCh38)
- Gene constraint
- LOEUF 0.057 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Similar variants
- NIPBL c.3304+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NIPBL c.358+1G>T Pathogenic ★★ same condition
- NIPBL c.3855+5G>A Pathogenic/Likely pathogenic ★★ same condition
- NIPBL c.5329-15A>G Pathogenic ★★ same condition
- NIPBL c.5575-1G>A Likely pathogenic ★★ same condition
- NIPBL c.5709+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NIPBL c.5808+1G>A Pathogenic ★★ same condition
- NIPBL c.5862+1G>A Pathogenic/Likely 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/nipbl-p-pro464 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown