Is NSD2 p.Arg548fs (c.1641_1642del) pathogenic?

NSD2 p.Arg548fs (c.16411642del) is classified Pathogenic in NSD2 (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with Rauch-Steindl syndrome.

What condition is associated with NSD2 p.Arg548fs (c.1641_1642del)?

NSD2 p.Arg548fs (c.1641_1642del) is associated with Rauch-Steindl syndrome (ClinVar).

How common is NSD2 p.Arg548fs (c.1641_1642del) in the general population?

NSD2 p.Arg548fs (c.1641_1642del) is no gnomAD frequency available for this variant (gnomAD).

NSD2 p.Arg548fs

c.1641_1642del · rs1577484648 · VCV2584449

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

Rauch-Steindl syndrome

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 7 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP -0.4, 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.Arg548fs
Coding: c.1641_1642del
MANE Select: NM_001042424
dbSNP: rs1577484648
Type: Deletion
Location: chr4:1935227 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 548: the 'disordered' region

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.Pro1343fs Pathogenic/Likely pathogenic ★★ same condition
NSD2 p.Asp215fs Pathogenic ★ same condition
NSD2 p.Asp726fs Likely pathogenic ★ same condition
NSD2 p.Cys1183fs Likely pathogenic ★ same condition
NSD2 p.Gln982fs Likely pathogenic ★ same condition
NSD2 p.Glu1100fs Pathogenic ★ same condition
NSD2 p.Glu1279fs Likely pathogenic ★ same condition
NSD2 p.Glu650fs 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-arg548fs (accessed [today's date]).

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