Is NSD2 p.Asp455fs (c.1363_1364dup) pathogenic?

NSD2 p.Asp455fs (c.13631364dup) is classified Pathogenic in NSD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-02). No gnomAD frequency available for this variant; Associated with syndromic intellectual disability.

What condition is associated with NSD2 p.Asp455fs (c.1363_1364dup)?

NSD2 p.Asp455fs (c.1363_1364dup) is associated with syndromic intellectual disability (ClinVar).

How common is NSD2 p.Asp455fs (c.1363_1364dup) in the general population?

NSD2 p.Asp455fs (c.1363_1364dup) is no gnomAD frequency available for this variant (gnomAD).

NSD2 p.Asp455fs

c.1363_1364dup · rs2108805708 · VCV1220533

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

syndromic intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.6	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NSD2
Protein: p.Asp455fs
Coding: c.1363_1364dup
MANE Select: NM_001042424
dbSNP: rs2108805708
Type: Microsatellite
Location: chr4:1918573 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 455: the 'disordered' region; a DNA-binding region

Full NSD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

syndromic intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NSD2 p.Asp455Gly Uncertain significance ★★ ⚠ same residue
NSD2 p.Phe922Ser Uncertain significance ★★ ⚠ same condition
NSD2 p.Lys530fs Likely pathogenic same condition
NSD2 c.1676_1679del Pathogenic ★★ same type
NSD2 p.Glu368fs Pathogenic ★★ same type
NSD2 p.Arg1360fs Uncertain significance ★★ same type
NSD2 p.Glu1101del Pathogenic ★ same type
NSD2 p.Glu1239fs Likely pathogenic ★ same type

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/nsd2-p-asp455fs (accessed [today's date]).

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