Is NIPBL p.Ser161= (c.483C>T) pathogenic?

NIPBL p.Ser161= (c.483C>T) is classified Benign/Likely benign in NIPBL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-13). Rare (popmax 0.193%, sas); Associated with Cornelia de Lange syndrome 1.

What condition is associated with NIPBL p.Ser161= (c.483C>T)?

NIPBL p.Ser161= (c.483C>T) is associated with Cornelia de Lange syndrome 1 (ClinVar).

How common is NIPBL p.Ser161= (c.483C>T) in the general population?

NIPBL p.Ser161= (c.483C>T) is rare (popmax 0.193%, sas) (gnomAD).

NIPBL p.Ser161=

c.483C>T · rs536895037 · VCV1743476

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.193%, sas)

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 7.7	GERP 2.6, phastCons 1
Overall
CADD	14.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.193% South Asian · 176/91,088 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.161%

Overall 0.0126% 204/1,614,100 alleles · rare exomes 186/1,461,826 · genomes 18/152,274 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.193%	518
Remaining individualsnot grpmax-eligible	0.0192%	5,209
East Asian	0.00223%	44,878
European (non-Finnish)	0.00127%	78,666

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.Ser161=
Coding: c.483C>T
MANE Select: NM_133433
dbSNP: rs536895037
Type: single nucleotide variant
Location: chr5:36962147 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 161: the 'disordered' region

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-ser161 (accessed [today's date]).

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