Is NSD2 p.Phe880fs (c.2639del) pathogenic?

NSD2 p.Phe880fs (c.2639del) is classified Likely pathogenic in NSD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-17). No gnomAD frequency available for this variant; Associated with Wolf-Hirschhorn like syndrome.

What condition is associated with NSD2 p.Phe880fs (c.2639del)?

NSD2 p.Phe880fs (c.2639del) is associated with Wolf-Hirschhorn like syndrome (ClinVar).

How common is NSD2 p.Phe880fs (c.2639del) in the general population?

NSD2 p.Phe880fs (c.2639del) is no gnomAD frequency available for this variant (gnomAD).

NSD2 p.Phe880fs

c.2639del · rs2108958731 · VCV1098704

Likely pathogenic Single submitter

Classification

Likely 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

Wolf-Hirschhorn like 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 14 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.43	GERP 0.88, phastCons 0.048

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.Phe880fs
Coding: c.2639del
MANE Select: NM_001042424
dbSNP: rs2108958731
Type: Deletion
Location: chr4:1955812 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.22 · 24 PDB
Residue 880: 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

Wolf-Hirschhorn like syndrome

Similar variants

NSD2 p.Ala429fs Likely pathogenic ★ same condition
NSD2 p.Gly107fs Likely pathogenic ★ same condition
NSD2 p.Ile954fs Likely pathogenic ★ same condition
NSD2 p.Leu353fs Likely pathogenic ★ same condition
NSD2 p.Cys207fs Pathogenic same condition
NSD2 c.1675-10del Likely benign same condition
NSD2 c.1675-11_1675-10del Likely benign same condition
NSD2 c.1675-12_1675-10del Likely benign 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-phe880fs (accessed [today's date]).

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