Is NSD2 p.Pro938fs (c.2813del) pathogenic?

NSD2 p.Pro938fs (c.2813del) is classified Likely pathogenic in NSD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-10). Associated with Rauch-Steindl syndrome.

What condition is associated with NSD2 p.Pro938fs (c.2813del)?

NSD2 p.Pro938fs (c.2813del) is associated with Rauch-Steindl syndrome (ClinVar).

NSD2 p.Pro938fs

c.2813del · VCV4056687

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 15 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: NSD2
Protein: p.Pro938fs
Coding: c.2813del
MANE Select: NM_001042424
Type: Deletion
Location: chr4:1956118 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 938: the pwwp 2 domain; 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.Pro1343fs Pathogenic/Likely pathogenic ★★ same condition
NSD2 p.Pro938= Benign ★★ same residue
NSD2 p.Arg548fs 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

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-pro938fs (accessed [today's date]).

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