Is NIPBL p.2508DS[3] (c.7524TTCAGA[3]) pathogenic?

NIPBL p.2508DS[3] (c.7524TTCAGA[3]) is classified Conflicting classifications of pathogenicity in NIPBL (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-28). Ultra-rare (popmax 0.0373%, afr); Associated with Inborn genetic diseases.

What condition is associated with NIPBL p.2508DS[3] (c.7524TTCAGA[3])?

NIPBL p.2508DS[3] (c.7524TTCAGA[3]) is associated with Inborn genetic diseases, intellectual disability, Cornelia de Lange syndrome 1 (ClinVar).

How common is NIPBL p.2508DS[3] (c.7524TTCAGA[3]) in the general population?

NIPBL p.2508DS[3] (c.7524TTCAGA[3]) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

NIPBL p.2508DS[3]

c.7524TTCAGA[3] · rs587784044 · VCV159231

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	phastCons 1
Overall
CADD	18.98	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(AGATTC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% African / African-American · 28/75,042 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0128% 206/1,614,156 alleles · ultra-rare exomes 171/1,461,878 · genomes 35/152,278 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,680
South Asian	0.0176%	5,693
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,251
East Asian	0.0134%	7,478
European (non-Finnish)	0.0117%	8,551
Admixed American	0.00833%	12,004
Finnishnot grpmax-eligible	0.00312%	32,019

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.2508DS[3]
Coding: c.7524TTCAGA[3]
MANE Select: NM_133433
dbSNP: rs587784044
Type: Microsatellite
Location: chr5:37059001 (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: intellectual disability Cornelia de Lange syndrome 1

Similar variants

NIPBL p.Arg1381fs Pathogenic ★★ same condition
NIPBL p.Arg2480fs Pathogenic ★★ same condition
NIPBL p.Asn2218del Pathogenic ★★ same condition
NIPBL p.Gln1595_Phe1596insTer Pathogenic ★★ same condition
NIPBL p.Glu1021fs Pathogenic ★★ same condition
NIPBL p.Glu1602fs Pathogenic ★★ same condition
NIPBL p.Glu2244del Likely pathogenic ★★ same condition
NIPBL p.Glu483fs 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-2508ds-3 (accessed [today's date]).

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