Is NIPBL p.Pro2017= (c.6051C>G) pathogenic?

NIPBL p.Pro2017= (c.6051C>G) is classified Likely benign in NIPBL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-16). Very rare (popmax 0.005%, amr); Associated with Cornelia de Lange syndrome 1.

What condition is associated with NIPBL p.Pro2017= (c.6051C>G)?

NIPBL p.Pro2017= (c.6051C>G) is associated with Cornelia de Lange syndrome 1 (ClinVar).

How common is NIPBL p.Pro2017= (c.6051C>G) in the general population?

NIPBL p.Pro2017= (c.6051C>G) is very rare (popmax 0.005%, amr) (gnomAD).

NIPBL p.Pro2017=

c.6051C>G · rs1031417413 · VCV2165148

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Cornelia de Lange syndrome 1

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 1.5	GERP 0.98, phastCons 1
Overall
CADD	9.526	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,984 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,613,600 alleles · very rare exomes 3/1,461,526 · genomes 1/152,074 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,995
European (non-Finnish)	8.48e-05%	1,179,848

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.Pro2017=
Coding: c.6051C>G
MANE Select: NM_133433
dbSNP: rs1031417413
Type: single nucleotide variant
Location: chr5:37038681 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full NIPBL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cornelia de Lange syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro2017 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown