Is NIPBL p.Val99= (c.297C>T) pathogenic?

NIPBL p.Val99= (c.297C>T) is classified Likely benign in NIPBL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). Absent from gnomAD v4.1; Associated with Cornelia de Lange syndrome 1.

What condition is associated with NIPBL p.Val99= (c.297C>T)?

NIPBL p.Val99= (c.297C>T) is associated with Cornelia de Lange syndrome 1 (ClinVar).

How common is NIPBL p.Val99= (c.297C>T) in the general population?

NIPBL p.Val99= (c.297C>T) is absent from gnomAD v4.1 (gnomAD).

NIPBL p.Val99=

c.297C>T · rs749086242 · VCV2985408

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.2	GERP 0.49, phastCons 1
Overall
CADD	8.508	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NIPBL
Protein: p.Val99=
Coding: c.297C>T
MANE Select: NM_133433
dbSNP: rs749086242
Type: single nucleotide variant
Location: chr5:36958170 (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 p.Val99Ile Uncertain significance ★ ⚠ same residue
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

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-val99 (accessed [today's date]).

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