Is NSD2 p.Arg600Ter (c.1798C>T) pathogenic?

NSD2 p.Arg600Ter (c.1798C>T) is classified Pathogenic in NSD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). Very rare (popmax 8.47e-05%, nfe); Associated with Rauch-Steindl syndrome.

What condition is associated with NSD2 p.Arg600Ter (c.1798C>T)?

NSD2 p.Arg600Ter (c.1798C>T) is associated with Rauch-Steindl syndrome (ClinVar).

How common is NSD2 p.Arg600Ter (c.1798C>T) in the general population?

NSD2 p.Arg600Ter (c.1798C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

NSD2 p.Arg600Ter

c.1798C>T · VCV3897864

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Rauch-Steindl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 22
REVEL	0.099	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.56, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.2e-05% 1/1,614,176 alleles · very rare exomes 1/1,461,888 · genomes 0/152,288 · joint denominator

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: NSD2
Protein: p.Arg600Ter
Coding: c.1798C>T
MANE Select: NM_001042424
Type: single nucleotide variant
Location: chr4:1939695 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 600: the 'disordered' region; a UniProt-annotated variant site (in raust)

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

Disease context

Rauch-Steindl syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NSD2 p.Arg450Ter Likely pathogenic ★★ same condition
NSD2 p.Arg755Ter Pathogenic/Likely pathogenic ★★ same condition
NSD2 p.Arg935Ter Pathogenic ★★ same condition
NSD2 p.Glu1363Lys Uncertain significance ★★ ⚠ same condition
NSD2 p.Phe922Ser Uncertain significance ★★ ⚠ same condition
NSD2 p.Val435Ala Uncertain significance ★★ ⚠ same condition
NSD2 p.Pro1341= Benign/Likely benign ★★ same condition
NSD2 c.2339-1G>A 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/nsd2-p-arg600ter (accessed [today's date]).

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