NIPBL p.Pro33=
c.99T>C · rs1232312013 · VCV2107292
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 | all four deltas below 0.2 · T>A here scores Δ0.82 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 13.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,024 alleles
Overall
6.2e-05%
1/1,614,012 alleles · very rare
exomes 1/1,461,674 · genomes 0/152,338 · 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
- NIPBL
- Protein
- p.Pro33=
- Coding
- c.99T>C
- MANE Select
- NM_133433
- dbSNP
- rs1232312013
- Type
- single nucleotide variant
- Location
- chr5:36955506 (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-pro33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown