Is NIPBL p.Ser352= (c.1056C>T) pathogenic?

NIPBL p.Ser352= (c.1056C>T) is classified Benign/Likely benign in NIPBL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0626%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NIPBL p.Ser352= (c.1056C>T)?

NIPBL p.Ser352= (c.1056C>T) is associated with Inborn genetic diseases, Cornelia de Lange syndrome 1 (ClinVar).

How common is NIPBL p.Ser352= (c.1056C>T) in the general population?

NIPBL p.Ser352= (c.1056C>T) is ultra-rare (popmax 0.0626%, nfe) (gnomAD).

NIPBL p.Ser352=

c.1056C>T · rs200440893 · VCV159026

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, nfe)

Conditions

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 0.2	GERP 2.6, phastCons 0.97
Overall
CADD	9.455	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% European (non-Finnish) · 739/1,179,894 alleles

Filtering AF 0.0589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0574%

Overall 0.0478% 771/1,613,922 alleles · ultra-rare exomes 750/1,461,716 · genomes 21/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0626%	1,597
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Finnishnot grpmax-eligible	0.0172%	5,820
Admixed American	0.00333%	29,985
African / African-American	0.00133%	75,022

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.Ser352=
Coding: c.1056C>T
MANE Select: NM_133433
dbSNP: rs200440893
Type: single nucleotide variant
Location: chr5:36975963 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cornelia de Lange syndrome 1

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-ser352 (accessed [today's date]).

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